20 results on '"Tang, Zhanyun"'
Search Results
2. The Mediator subunit MED23 couples H2B mono-ubiquitination to transcriptional control and cell fate determination.
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Yao, Xiao, Tang, Zhanyun, Fu, Xing, Yin, Jingwen, Liang, Yan, Li, Chonghui, Li, Huayun, Tian, Qing, Roeder, Robert G, and Wang, Gang
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UBIQUITINATION , *GENETIC transcription , *CELL differentiation , *TRANSCRIPTION factors , *MASS spectrometry - Abstract
The Mediator complex orchestrates multiple transcription factors with the Pol II apparatus for precise transcriptional control. However, its interplay with the surrounding chromatin remains poorly understood. Here, we analyze differential histone modifications between WT and MED23-/- (KO) cells and identify H2B mono-ubiquitination at lysine 120 (H2Bub) as a MED23-dependent histone modification. Using tandem affinity purification and mass spectrometry, we find that MED23 associates with the RNF20/40 complex, the enzyme for H2Bub, and show that this association is critical for the recruitment of RNF20/40 to chromatin. In a cell-free system, Mediator directly and substantially increases H2Bub on recombinant chromatin through its cooperation with RNF20/40 and the PAF complex. Integrative genome-wide analyses show that MED23 depletion specifically reduces H2Bub on a subset of MED23-controlled genes. Importantly, MED23-coupled H2Bub levels are oppositely regulated during myogenesis and lung carcinogenesis. In sum, these results establish a mechanistic link between the Mediator complex and a critical chromatin modification in coordinating transcription with cell growth and differentiation. [ABSTRACT FROM AUTHOR]
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- 2015
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3. Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation.
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Sabari, Benjamin R., Tang, Zhanyun, Huang, He, Yong-Gonzalez, Vladimir, Molina, Henrik, Kong, Ha Eun, Dai, Lunzhi, Shimada, Miho, Cross, Justin R., Zhao, Yingming, Roeder, Robert G., and Allis, C. David
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GENETIC transcription , *HISTONE acetylation , *DNA , *ACYL group , *ACETYLTRANSFERASES , *GENE expression , *CATALYTIC activity - Abstract
Summary Acetylation of histones at DNA regulatory elements plays a critical role in transcriptional activation. Histones are also modified by other acyl moieties, including crotonyl, yet the mechanisms that govern acetylation versus crotonylation and the functional consequences of this “choice” remain unclear. We show that the coactivator p300 has both crotonyltransferase and acetyltransferase activities, and that p300-catalyzed histone crotonylation directly stimulates transcription to a greater degree than histone acetylation. Levels of histone crotonylation are regulated by the cellular concentration of crotonyl-CoA, which can be altered through genetic and environmental perturbations. In a cell-based model of transcriptional activation, increasing or decreasing the cellular concentration of crotonyl-CoA leads to enhanced or diminished gene expression, respectively, which correlates with the levels of histone crotonylation flanking the regulatory elements of activated genes. Our findings support a general principle wherein differential histone acylation (i.e., acetylation versus crotonylation) couples cellular metabolism to the regulation of gene expression. [ABSTRACT FROM AUTHOR]
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- 2015
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4. SET1 and p300 Act Synergistically, through Coupled Histone Modifications, in Transcriptional Activation by p53.
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Tang, Zhanyun, Chen, Wei-Yi, Shimada, Miho, Nguyen, Uyen?T.T., Kim, Jaehoon, Sun, Xiao-Jian, Sengoku, Toru, McGinty, Robert?K., Fernandez, Joseph?P., Muir, Tom?W., and Roeder, Robert?G.
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P53 antioncogene , *GENETIC transcription , *HISTONE genetics , *HUMAN chromatin , *ROBUST control , *ACETYLATION , *DNA damage - Abstract
Summary: The H3K4me3 mark in chromatin is closely correlated with actively transcribed genes, although the mechanisms involved in its generation and function are not fully understood. In vitro studies with recombinant chromatin and purified human factors demonstrate a robust SET1 complex (SET1C)-mediated H3K4 trimethylation that is dependent upon p53- and p300-mediated H3 acetylation, a corresponding SET1C-mediated enhancement of p53- and p300-dependent transcription that reflects a primary effect of SET1C through H3K4 trimethylation, and direct SET1C-p53 and SET1C-p300 interactions indicative of a targeted recruitment mechanism. Complementary cell-based assays demonstrate a DNA-damage-induced p53-SET1C interaction, a corresponding enrichment of SET1C and H3K4me3 on a p53 target gene (p21/WAF1), and a corresponding codependency of H3K4 trimethylation and transcription upon p300 and SET1C. These results establish a mechanism in which SET1C and p300 act cooperatively, through direct interactions and coupled histone modifications, to facilitate the function of p53. [Copyright &y& Elsevier]
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- 2013
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5. PP2A Is Required for Centromeric Localization of Sgo1 and Proper Chromosome Segregation
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Tang, Zhanyun, Shu, Hongjun, Qi, Wei, Mahmood, Nadir A., Mumby, Marc C., and Yu, Hongtao
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CHROMOSOMES , *MITOSIS , *CELLS , *VERTEBRATES , *PHOSPHORYLATION , *PHOSPHOPROTEIN phosphatases - Abstract
Summary: Loss of sister-chromatid cohesion triggers chromosome segregation in mitosis and occurs through two mechanisms in vertebrate cells: (1) phosphorylation and removal of cohesin from chromosome arms by mitotic kinases, including Plk1, during prophase, and (2) cleavage of centromeric cohesin by separase at the metaphase-anaphase transition. Bub1 and the MEI-S332/Shugoshin (Sgo1) family of proteins protect centromeric cohesin from mitotic kinases during prophase. We show that human Sgo1 binds to protein phosphatase 2A (PP2A). PP2A localizes to centromeres in a Bub1-dependent manner. The Sgo1–PP2A interaction is required for centromeric localization of Sgo1 and proper chromosome segregation in human cells. Depletion of Plk1 by RNA interference (RNAi) restores centromeric localization of Sgo1 and prevents chromosome missegregation in cells depleted of PP2A_Aα. Our findings suggest that Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting Plk1-mediated chromosome removal of Sgo1. [Copyright &y& Elsevier]
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- 2006
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6. Human Bub1 protects centromeric sister-chromatid cohesion through Shugoshin during mitosis.
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Tang, Zhanyun, Sun, Yuxiao, Harley, Sara E., Zou, Hui, and Yu, Hongtao
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SISTER chromatid exchange , *CELLS , *CHROMOSOMES , *RNA , *MITOSIS , *RIBOSE - Abstract
Sister chromatids in mammalian cells remain attached mostly at their centromeres at metaphase because of the loss of cohesion along chromosome arms in prophase. Here, we report that Bub1 retains centromeric cohesion in mitosis of human cells. Depletion of Bub1 or Shugoshin (Sgo1) in HeLa cells by RNA interference causes massive missegregation of sister chromatids that originates at centromeres. Surprisingly, loss of chromatid cohesion in Bubi and Sgo1 RNA-interference cells does not appear to require the full activation of separase but, instead, triggers a mitotic arrest that depends on Mad2 and Aurora B. Bub1 maintains the steady-state levels and centromeric localization of Sgo1. Therefore, Bub1 protects centromeric cohesion through Shugoshin in mitosis. [ABSTRACT FROM AUTHOR]
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- 2004
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7. Phosphorylation of Cdc20 by Bub1 Provides a Catalytic Mechanism for APC/C Inhibition by the Spindle Checkpoint
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Tang, Zhanyun, Shu, Hongjun, Oncel, Dilhan, Chen, She, and Yu, Hongtao
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CHEMICAL reactions , *PHOSPHORYLATION , *CLONE cells , *NUCLEIC acids , *CELL division - Abstract
To ensure the fidelity of chromosome segregation, the spindle checkpoint blocks the ubiquitin ligase activity of APC/CCdc20 in response to a single chromatid not properly attached to the mitotic spindle. Here we show that HeLa cells depleted for Bub1 by RNA interference are defective in checkpoint signaling. Bub1 directly phosphorylates Cdc20 in vitro and inhibits the ubiquitin ligase activity of APC/CCdc20 catalytically. A Cdc20 mutant with all six Bub1 phosphorylation sites removed is refractory to Bub1-mediated phosphorylation and inhibition in vitro. Upon checkpoint activation, Bub1 itself is hyperphosphorylated and its kinase activity toward Cdc20 is stimulated. Ectopic expression of the nonphosphorylatable Cdc20 mutant allows HeLa cells to escape from mitosis in the presence of spindle damage. Therefore, Bub1-mediated phosphorylation of Cdc20 is required for proper checkpoint signaling. We speculate that inhibition of APC/CCdc20 by Bub1 in a catalytic fashion may partly account for the exquisite sensitivity of the spindle checkpoint. [Copyright &y& Elsevier]
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- 2004
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8. The Mad2 spindle checkpoint protein has two distinct natively folded states.
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Luo, Xuelian, Tang, Zhanyun, Xia, Guohong, Wassmann, Katja, Matsumoto, Tomohiro, Rizo, Josep, and Yu, Hongtao
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GENETICS , *CHROMOSOMES , *PROTEINS , *NUCLEAR magnetic resonance spectroscopy , *CELLS , *MITOSIS - Abstract
The spindle checkpoint delays chromosome segregation in response to misaligned sister chromatids during mitosis, thus ensuring the fidelity of chromosome inheritance. Through binding to Cdc20, the Mad2 spindle checkpoint protein inhibits the target of this checkpoint, the ubiquitin protein ligase APC/CCdc20. We now show that without cofactor binding or covalent modification Mad2 adopts two distinct folded conformations at equilibrium (termed N1-Mad2 and N2-Mad2). The structure of N2-Mad2 has been determined by NMR spectroscopy. N2-Mad2 is much more potent in APC/C inhibition. Overexpression of a Mad2 mutant that specifically sequesters N2-Mad2 partially blocks checkpoint signaling in living cells. The two Mad2 conformers interconvert slowly in vitro, but interconversion is accelerated by a fragment of Mad1, an upstream regulator of Mad2. Our results suggest that the unusual two-state behavior of Mad2 is critical for spindle checkpoint signaling. [ABSTRACT FROM AUTHOR]
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- 2004
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9. The Mad2 Spindle Checkpoint Protein Undergoes Similar Major Conformational Changes Upon Binding to Either Mad1 or Cdc20
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Luo, Xuelian, Tang, Zhanyun, Rizo, Josep, and Yu, Hongtao
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PROTEINS , *BIOLOGY - Abstract
Mad2 participates in spindle checkpoint inhibition of APCCdc20. We show that RNAi-mediated suppression of Mad1 function in mammalian cells causes loss of Mad2 kinetochore localization and impairment of the spindle checkpoint. Mad1 and Cdc20 contain Mad2 binding motifs that share a common consensus. We have identified a class of Mad2 binding peptides with a similar consensus. Binding of one of these ligands, MBP1, triggers an extensive rearrangement of the tertiary structure of Mad2. Mad2 also undergoes a similar striking structural change upon binding to a Mad1 or Cdc20 binding motif peptide. Our data suggest that, upon checkpoint activation, Mad1 recruits Mad2 to unattached kinetochores and may promote binding of Mad2 to Cdc20. [Copyright &y& Elsevier]
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- 2002
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10. A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription.
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Wang, Shu-Ping, Tang, Zhanyun, Chen, Chun-Wei, Shimada, Miho, Koche, Richard P., Wang, Lan-Hsin, Nakadai, Tomoyoshi, Chramiec, Alan, Krivtsov, Andrei V., Armstrong, Scott A., and Roeder, Robert G.
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GENETIC regulation , *GENE enhancers , *CHROMATIN , *METHYLTRANSFERASES , *GENETIC transcription - Abstract
Summary Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1 + /H3K27ac + ) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription. The UTX-MLL4 complex enhances p300-dependent H3K27 acetylation through UTX-dependent stimulation of p300 recruitment, while MLL4-mediated H3K4 monomethylation, reciprocally, requires p300 function. Importantly, MLL4-generated H3K4me1 further enhances p300-dependent transcription. This work reveals a previously unrecognized cooperativity among enhancer-associated chromatin modulators, including a unique function for UTX, in establishing an “active enhancer landscape” and defines a detailed mechanism for the joint deposition of H3K4me1 and H3K27ac. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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11. Cooperation between IRTKS and deubiquitinase OTUD4 enhances the SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression.
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Cui, Xiaofang, Shang, Xueying, Xie, Jia, Xie, Chenyi, Tang, Zhanyun, Luo, Qing, Wu, Chongchao, Wang, Guangxing, Wang, Na, He, Kunyan, Wang, Lan, Huang, Liyu, Wan, Bingbing, Roeder, Robert G., and Han, Ze-Guang
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GENE expression , *METASTASIS , *CADHERINS , *CANCER invasiveness , *EPITHELIAL-mesenchymal transition - Abstract
Elevated expression and genetic aberration of IRTKS, also named as BAIAP2L1, have been observed in many tumors, especially in tumor progression. however, the molecular and cellular mechanisms involved in the IRTKS-enhanced tumor progression are obscure. Here we show that higher IRTKS level specifically increases histone H3 lysine 9 trimethylation (H3K9me3) by promoting accumulation of the histone methyltransferase SETDB1. Furthermore, we reveal that IRTKS recruits the deubiquitinase OTUD4 to remove Lys48-linked polyubiquitination at K182/K1050 sites of SETDB1, thus blocking SETDB1 degradation via the ubiquitin-proteasome pathway. Interestingly, the enhanced IRTKS–OTUD4–SETDB1–H3K9me3 axis leads to a general decrease in chromatin accessibility, which inhibits transcription of CDH1 encoding E-cadherin, a key molecule essential for maintaining epithelial cell phenotype, and therefore results in epithelial-mesenchymal transition (EMT) and malignant cell metastasis. Clinically, the elevated IRTKS levels in tumor specimens correlate with SETDB1 levels, but negatively associate with survival time. Our data reveal a novel mechanism for the IRTKS-enhanced tumor progression, where IRTKS cooperates with OTUD4 to enhance SETDB1-mediated H3K9 trimethylation that promotes tumor metastasis via suppressing E-cadherin expression. This study also provides a potential approach to reduce the activity and stability of the known therapeutic target SETDB1 possibly through regulating IRTKS or deubiquitinase OTUD4. • Higher levels of IRTKS increase H3K9me3 by promoting SETDB1 accuumulation. • IRTKS recruits the deubiquitinase OTUD4 to blocking SETDB1 degradation. • The enhanced IRTKS–OTUD4–SETDB1–H3K9me3 axis decreases chromatin accessibility, and inhibits E-cadherin transcription, resulting in EMT and tumor metastasis. • Clinically, elevated IRTKS levels in tumor correlate with SETDB1 levels, and negatively associate with survival time. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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12. Dynamic Competing Histone H4 K5K8 Acetylation and Butyrylation Are Hallmarks of Highly Active Gene Promoters.
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Goudarzi, Afsaneh, Zhang, Di, Huang, He, Barral, Sophie, Kwon, Oh Kwang, Qi, Shankang, Tang, Zhanyun, Buchou, Thierry, Vitte, Anne-Laure, He, Tieming, Cheng, Zhongyi, Montellier, Emilie, Gaucher, Jonathan, Curtet, Sandrine, Debernardi, Alexandra, Charbonnier, Guillaume, Puthier, Denis, Petosa, Carlo, Panne, Daniel, and Rousseaux, Sophie
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HISTONES , *ACETYLATION , *PROMOTERS (Genetics) , *CHROMATIN , *GENE expression - Abstract
Summary Recently discovered histone lysine acylation marks increase the functional diversity of nucleosomes well beyond acetylation. Here, we focus on histone butyrylation in the context of sperm cell differentiation. Specifically, we investigate the butyrylation of histone H4 lysine 5 and 8 at gene promoters where acetylation guides the binding of Brdt, a bromodomain-containing protein, thereby mediating stage-specific gene expression programs and post-meiotic chromatin reorganization. Genome-wide mapping data show that highly active Brdt-bound gene promoters systematically harbor competing histone acetylation and butyrylation marks at H4 K5 and H4 K8. Despite acting as a direct stimulator of transcription, histone butyrylation competes with acetylation, especially at H4 K5, to prevent Brdt binding. Additionally, H4 K5K8 butyrylation also marks retarded histone removal during late spermatogenesis. Hence, alternating H4 acetylation and butyrylation, while sustaining direct gene activation and dynamic bromodomain binding, could impact the final male epigenome features. [ABSTRACT FROM AUTHOR]
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- 2016
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13. Metabolic Regulation of Gene Expression by Histone Lysine β-Hydroxybutyrylation.
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Xie, Zhongyu, Zhang, Di, Chung, Dongjun, Tang, Zhanyun, Huang, He, Dai, Lunzhi, Qi, Shankang, Li, Jingya, Colak, Gozde, Chen, Yue, Xia, Chunmei, Peng, Chao, Ruan, Haibin, Kirkey, Matt, Wang, Danli, Jensen, Lindy M., Kwon, Oh Kwang, Lee, Sangkyu, Pletcher, Scott D., and Tan, Minjia
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METABOLIC regulation , *GENE expression , *HISTONES , *STREPTOZOTOCIN , *PATHOLOGICAL physiology - Abstract
Summary Here we report the identification and verification of a β-hydroxybutyrate-derived protein modification, lysine β-hydroxybutyrylation (Kbhb), as a new type of histone mark. Histone Kbhb marks are dramatically induced in response to elevated β-hydroxybutyrate levels in cultured cells and in livers from mice subjected to prolonged fasting or streptozotocin-induced diabetic ketoacidosis. In total, we identified 44 histone Kbhb sites, a figure comparable to the known number of histone acetylation sites. By ChIP-seq and RNA-seq analysis, we demonstrate that histone Kbhb is a mark enriched in active gene promoters and that the increased H3K9bhb levels that occur during starvation are associated with genes upregulated in starvation-responsive metabolic pathways. Histone β-hydroxybutyrylation thus represents a new epigenetic regulatory mark that couples metabolism to gene expression, offering a new avenue to study chromatin regulation and diverse functions of β-hydroxybutyrate in the context of important human pathophysiological states, including diabetes, epilepsy, and neoplasia. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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14. Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain.
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Li, Yuanyuan, Sabari, Benjamin R., Panchenko, Tatyana, Wen, Hong, Zhao, Dan, Guan, Haipeng, Wan, Liling, Huang, He, Tang, Zhanyun, Zhao, Yingming, Roeder, Robert G., Shi, Xiaobing, Allis, C. David, and Li, Haitao
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COUPLING reactions (Chemistry) , *HISTONES , *GENETIC transcription , *COVALENT bonds , *CHROMATIN - Abstract
Summary Recognition of histone covalent modifications by chromatin-binding protein modules (“readers”) constitutes a major mechanism for epigenetic regulation, typified by bromodomains that bind acetyllysine. Non-acetyl histone lysine acylations (e.g., crotonylation, butyrylation, propionylation) have been recently identified, but readers that prefer these acylations have not been characterized. Here we report that the AF9 YEATS domain displays selectively higher binding affinity for crotonyllysine over acetyllysine. Structural studies revealed an extended aromatic sandwiching cage with crotonyl specificity arising from π-aromatic and hydrophobic interactions between crotonyl and aromatic rings. These features are conserved among the YEATS, but not the bromodomains. Using a cell-based model, we showed that AF9 co-localizes with crotonylated histone H3 and positively regulates gene expression in a YEATS domain-dependent manner. Our studies define the evolutionarily conserved YEATS domain as a family of crotonyllysine readers and specifically demonstrate that the YEATS domain of AF9 directly links histone crotonylation to active transcription. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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15. Regulation of transcription by the MLL2 complex and MLL complex-associated AKAP95.
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Jiang, Hao, Lu, Xiangdong, Shimada, Miho, Dou, Yali, Tang, Zhanyun, and Roeder, Robert G
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GENETIC regulation , *HISTONES , *METHYLATION , *GENE expression , *GENETIC transcription , *ADENOSYLMETHIONINE - Abstract
Although histone H3 Lys4 (H3K4) methylation is widely associated with gene activation, direct evidence for its causal role in transcription, through specific MLL family members, is scarce. Here we have purified a human MLL2 (Kmt2b) complex that is highly active in H3K4 methylation and chromatin transcription in a cell-free system. This effect requires S-adenosyl methionine and intact H3K4, thus establishing a direct and causal role for MLL2-mediated H3K4 methylation in transcription. We also show that human AKAP95, a chromatin-associated protein, physically and functionally associates with MLL complexes and directly enhances their methyltransferase activity. Ectopic AKAP95 stimulates expression of a chromosomal reporter gene in synergy with MLL1 or MLL2, whereas AKAP95 depletion impairs retinoic acid-mediated gene induction in embryonic stem cells. These results demonstrate an important role for AKAP95 in regulating histone methylation and gene expression, particularly during cell-fate transitions. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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16. A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis.
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Sun, Xiao-Jian, Wang, Zhanxin, Wang, Lan, Jiang, Yanwen, Kost, Nils, Soong, T. David, Chen, Wei-Yi, Tang, Zhanyun, Nakadai, Tomoyoshi, Elemento, Olivier, Fischle, Wolfgang, Melnick, Ari, Patel, Dinshaw J., Nimer, Stephen D., and Roeder, Robert G.
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TRANSCRIPTION factors , *NUCLEATION , *OLIGOMERS , *LEUKEMIA etiology , *HEMATOPOIETIC agents , *GENE expression - Abstract
Transcription factors are frequently altered in leukaemia through chromosomal translocation, mutation or aberrant expression. AML1-ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukaemia, is a transcription factor implicated in both gene repression and activation. AML1-ETO oligomerization, mediated by the NHR2 domain, is critical for leukaemogenesis, making it important to identify co-regulatory factors that 'read' the NHR2 oligomerization and contribute to leukaemogenesis. Here we show that, in human leukaemic cells, AML1-ETO resides in and functions through a stable AML1-ETO-containing transcription factor complex (AETFC) that contains several haematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukaemogenesis. Within the AETFC complex, AML1-ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins. Crystallographic analysis of the NHR2-N2B complex reveals a unique interaction pattern in which an N2B peptide makes direct contact with side chains of two NHR2 domains as a dimer, providing a novel model of how dimeric/oligomeric transcription factors create a new protein-binding interface through dimerization/oligomerization. Intriguingly, disruption of this interaction by point mutations abrogates AML1-ETO-induced haematopoietic stem/progenitor cell self-renewal and leukaemogenesis. These results reveal new mechanisms of action of AML1-ETO, and provide a potential therapeutic target in t(8;21)-positive acute myeloid leukaemia. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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17. USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage Differentiation and HoxB4 Transcription.
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Deng, Changwang, Li, Ying, Liang, Shermi, Cui, Kairong, Salz, Tal, Yang, Hui, Tang, Zhanyun, Gallagher, Patrick G., Qiu, Yi, Roeder, Robert, Zhao, Keji, Bungert, Jörg, and Huang, Suming
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EMBRYONIC stem cell research , *CELL proliferation , *RNA , *PROGENITOR cells , *TRANSCRIPTION factors - Abstract
The interplay between polycomb and trithorax complexes has been implicated in embryonic stem cell (ESC) self-renewal and differentiation. It has been shown recently that WRD5 and Dpy-30, specific components of the SET1/MLL protein complexes, play important roles during ESC self-renewal and differentiation of neural lineages. However, not much is known about how and where specific trithorax complexes are targeted to genes involved in self-renewal or lineage-specification. Here, we report that the recruitment of the hSET1A histone H3K4 methyltransferase (HMT) complex by transcription factor USF1 is required for mesoderm specification and lineage differentiation. In undifferentiated ESCs, USF1 maintains hematopoietic stem/progenitor cell (HS/PC) associated bivalent chromatin domains and differentiation potential. Furthermore, USF1 directed recruitment of the hSET1A complex to the HoxB4 promoter governs the transcriptional activation of HoxB4 gene and regulates the formation of early hematopoietic cell populations. Disruption of USF or hSET1A function by overexpression of a dominant-negative AUSF1 mutant or by RNA-interference-mediated knockdown, respectively, led to reduced expression of mesoderm markers and inhibition of lineage differentiation. We show that USF1 and hSET1A together regulate H3K4me3 modifications and transcription preinitiation complex assembly at the hematopoietic-associated HoxB4 gene during differentiation. Finally, ectopic expression of USF1 in ESCs promotes mesoderm differentiation and enforces the endothelial-to-hematopoietic transition by inducing hematopoietic-associated transcription factors, HoxB4 and TAL1. Taken together, our findings reveal that the guided-recruitment of the hSET1A histone methyltransferase complex and its H3K4 methyltransferase activity by transcription regulator USF1 safeguards hematopoietic transcription programs and enhances mesoderm/hematopoietic differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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18. H3K4me3 Interactions with TAF3 Regulate Preinitiation Complex Assembly and Selective Gene Activation
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Lauberth, Shannon M., Nakayama, Takahiro, Wu, Xiaolin, Ferris, Andrea L., Tang, Zhanyun, Hughes, Stephen H., and Roeder, Robert G.
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GENETIC regulation , *POST-translational modification , *TATA box-binding protein-associated factors , *GENETIC transcription regulation , *INITIATION factors (Biochemistry) genetics , *HISTONES , *CHROMATIN , *P53 protein - Abstract
Summary: Histone modifications regulate chromatin-dependent processes, yet the mechanisms by which they contribute to specific outcomes remain unclear. H3K4me3 is a prominent histone mark that is associated with active genes and promotes transcription through interactions with effector proteins that include initiation factor TFIID. We demonstrate that H3K4me3-TAF3 interactions direct global TFIID recruitment to active genes, some of which are p53 targets. Further analyses show that (1) H3K4me3 enhances p53-dependent transcription by stimulating preinitiation complex (PIC) formation; (2) H3K4me3, through TAF3 interactions, can act either independently or cooperatively with the TATA box to direct PIC formation and transcription; and (3) H3K4me3-TAF3/TFIID interactions regulate gene-selective functions of p53 in response to genotoxic stress. Our findings indicate a mechanism by which H3K4me3 directs PIC assembly for the rapid induction of specific p53 target genes. [Copyright &y& Elsevier]
- Published
- 2013
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19. RAD6-Mediated Transcription-Coupled H2B Ubiquitylation Directly Stimulates H3K4 Methylation in Human Cells
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Kim, Jaehoon, Guermah, Mohamed, McGinty, Robert K., Lee, Jung-Shin, Tang, Zhanyun, Milne, Thomas A., Shilatifard, Ali, Muir, Tom W., and Roeder, Robert G.
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TRANSCRIPTION factors , *METHYLATION , *MAMMALS , *LIGASES , *CHROMATIN , *GENETIC transcription - Abstract
Summary: H2B ubiquitylation has been implicated in active transcription but is not well understood in mammalian cells. Beyond earlier identification of hBRE1 as the E3 ligase for H2B ubiquitylation in human cells, we now show (1) that hRAD6 serves as the cognate E2-conjugating enzyme; (2) that hRAD6, through direct interaction with hPAF-bound hBRE1, is recruited to transcribed genes and ubiquitylates chromatinized H2B at lysine 120; (3) that hPAF-mediated transcription is required for efficient H2B ubiquitylation as a result of hPAF-dependent recruitment of hBRE1-hRAD6 to the Pol II transcription machinery; (4) that H2B ubiquitylation per se does not affect the level of hPAF-, SII-, and p300-dependent transcription and likely functions downstream; and (5) that H2B ubiquitylation directly stimulates hSET1-dependent H3K4 di- and trimethylation. These studies establish the natural H2B ubiquitylation factors in human cells and also detail the mechanistic basis for H2B ubiquitylation and function during transcription. [Copyright &y& Elsevier]
- Published
- 2009
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20. ATP Binding and ATP Hydrolysis Play Distinct Roles in the Function of 26S Proteasome
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Liu, Chang-Wei, Li, Xiaohua, Thompson, David, Wooding, Kerry, Chang, Tsui-ling, Tang, Zhanyun, Yu, Hongtao, Thomas, Philip J., and DeMartino, George N.
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ADENOSINE triphosphate , *HYDROLYSIS , *PROTEINS , *SOLVOLYSIS - Abstract
Summary: The 26S proteasome degrades polyubiquitinated proteins by an energy-dependent mechanism. Here we define multiple roles for ATP in 26S proteasome function. ATP binding is necessary and sufficient for assembly of 26S proteasome from 20S proteasome and PA700/19S subcomplexes and for proteasome activation. Proteasome assembly and activation may require distinct ATP binding events. The 26S proteasome degrades nonubiquitylated, unstructured proteins without ATP hydrolysis, indicating that substrate translocation per se does not require the energy of hydrolysis. Nonubiquitylated folded proteins and certain polyubiquitylated folded proteins were refractory to proteolysis. The latter were deubiquitylated by an ATP-independent mechanism. Other folded as well as unstructured polyubiquitylated proteins required ATP hydrolysis for proteolysis and deubiquitylation. Thus, ATP hydrolysis is not used solely for substrate unfolding. These results indicate that 26S proteasome-catalyzed degradation of polyubiquitylated proteins involves mechanistic coupling of several processes and that such coupling imposes an energy requirement not apparent for any isolated process. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
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