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Highlights: [•] G9a upregulates p21 expression independently of its HMTase activity. [•] Positive regulation of p21 by G9a is p53 independent. [•] G9a interacts with PCAF to activate p21 expression. [•] G9a and PCAF are recruited to p21 promoter upon etoposide treatment. [•] G9a inhibits cell survival via p21-mediated apoptosis upon cellular stress. [ABSTRACT FROM AUTHOR]

Histone methylation has diverse functions including transcriptional regulation via its lysine or arginine residue methylation. Studies indicate that deregulation of histone methylation is linked to human cancers including leukemia. Histone H3K27 methyltrnasferase response element II binding protein (RE-IIBP), as a transcriptional repressor to target gene IL-5, interacts with HDAC and is over-expressed in leukemia patient samples. In this study, we have identified that hematopoiesis-related genes GATA1 and HOXA9 are down-regulated by RE-IIBP in K562 and 293T cells. Transient reporter analysis revealed that GATA1 transcription was repressed by RE-IIBP. On the other hand, HOXA9 and PBX-related homeobox gene MEIS1 was up-regulated by RE-IIBP. These results suggest that RE-IIBP might have a role in hematopoiesis or leukemogenesis by regulating the transcription of target genes, possibly via its H3K27 methyltransferase activity. [ABSTRACT FROM AUTHOR]

Histone H3S10 phosphorylation has been known as a cell cycle-specific marker and has a role in transcriptional activation. Various kinases phosphorylate H3S10 in different species, however, the role of the mitotic serine/threonine protein kinase Aurora A (AURKA) is largely unknown. Here we present evidence that AURKA phosphorylates H3S10 and activates target gene transcription. We show that down-regulation of AURKA level during leukemia cell differentiation results in decreased H3S10 phosphorylation level. We further show that AURKA is recruited to target gene promoters and activates transcription via H3S10 phosphorylation. Furthermore, this recruitment can be disrupted by the AURKA inhibitor Alisertib and results in H3K9-me2 recruitment by G9a. [ABSTRACT FROM AUTHOR]

Abstract: Epigenetic modification plays an important role in transcriptional regulation. As a subunit of the INHAT (inhibitor of histone acetyltransferases) complex, SET/TAF-Iβ evidences transcriptional repression activity. In this study, we demonstrate that SET/TAF-Iβ is abundantly expressed in neuronal tissues of Drosophila embryos. It is expressed at high levels prior to and in early stages of neuronal development, and gradually reduced as differentiation proceeds. SET/TAF-Iβ binds to the promoters of a subset of neuronal development markers and negatively regulates the transcription of these genes. The results of this study show that the knockdown of SET/TAF-Iβ by si-RNA induces neuronal cell differentiation, thus implicating SET/TAF-Iβ as a negative regulator of neuronal development. [ABSTRACT FROM AUTHOR]

Abstract: Clonorchiasis is an infection associated with bile duct malignancy and subsequent development of cholangiocarcinoma. This disease is mainly caused by Clonorchis sinensis worms and their excretory–secretory products (ESP). However, the precise molecular mechanisms of carcinogenesis remain to be determined. Previously, we established differential gene expression profiles from microarrays containing 23,920 human genes of known function in a human cholangiocarcinoma cell line, HuCCT1, treated with ESP. Among the upregulated genes, we focused on minichromosome maintenance protein 7 (Mcm7), which is implicated in various cancer types, and analyzed transcriptional regulation mediated by ESP to further elucidate its role in cholangiocarcinoma development. Global histone acetylation levels were increased in ESP-treated cells, along with histone acetyltransferase (HAT) protein expression. Detailed promoter analysis using reporter and chromatin immunoprecipitation assays revealed that transcriptional activation of Mcm7 is mediated by HAT recruitment to the promoter region upon C. sinensis ESP treatment. These findings contribute to clarification of the intrinsic mechanism underlying the cellular carcinogenesis process stimulated by Mcm7 in C. sinensis-treated host cells. [Copyright &y& Elsevier]