Search

Your search keyword '"Blobel, Gerd A."' showing total 9 results
Start Over Author "Blobel, Gerd A." Journal nature genetics
9 results on '"Blobel, Gerd A."'

2. BRD4 orchestrates genome folding to promote neural crest differentiation

Author

Linares-Saldana, Ricardo, Kim, Wonho, Bolar, Nikhita A, Zhang, Haoyue, Koch-Bojalad, Bailey A, Yoon, Sora, Shah, Parisha P, Karnay, Ashley, Park, Daniel S, Luppino, Jennifer M, Nguyen, Son C, Padmanabhan, Arun, Smith, Cheryl L, Poleshko, Andrey, Wang, Qiaohong, Li, Li, Srivastava, Deepak, Vahedi, Golnaz, Eom, Gwang Hyeon, Blobel, Gerd A, Joyce, Eric F, and Jain, Rajan

Subjects
Human Genome, Neurosciences, Genetics, Pediatric, Brain Disorders, Underpinning research, 1.1 Normal biological development and functioning, Animals, Cell Cycle Proteins, Cell Differentiation, Chromatin, Chromosomal Proteins, Non-Histone, Gene Expression Regulation, Genome, HEK293 Cells, Humans, Hydrophobic and Hydrophilic Interactions, Integrases, Mice, Models, Biological, Mouse Embryonic Stem Cells, Muscle Cells, Neural Crest, Nuclear Proteins, Protein Binding, Protein Domains, Proteolysis, Transcription Factors, Transcription, Genetic, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Higher-order chromatin structure regulates gene expression, and mutations in proteins mediating genome folding underlie developmental disorders known as cohesinopathies. However, the relationship between three-dimensional genome organization and embryonic development remains unclear. Here we define a role for bromodomain-containing protein 4 (BRD4) in genome folding, and leverage it to understand the importance of genome folding in neural crest progenitor differentiation. Brd4 deletion in neural crest results in cohesinopathy-like phenotypes. BRD4 interacts with NIPBL, a cohesin agonist, and BRD4 depletion or loss of the BRD4-NIPBL interaction reduces NIPBL occupancy, suggesting that BRD4 stabilizes NIPBL on chromatin. Chromatin interaction mapping and imaging experiments demonstrate that BRD4 depletion results in compromised genome folding and loop extrusion. Finally, mutation of individual BRD4 amino acids that mediate an interaction with NIPBL impedes neural crest differentiation into smooth muscle. Remarkably, loss of WAPL, a cohesin antagonist, rescues attenuated smooth muscle differentiation resulting from BRD4 loss. Collectively, our data reveal that BRD4 choreographs genome folding and illustrates the relevance of balancing cohesin activity for progenitor differentiation.

Published
2021

9. Publisher Correction: BRD4 orchestrates genome folding to promote neural crest differentiation

Author

Linares-Saldana, Ricardo, Kim, Wonho, Bolar, Nikhita A., Zhang, Haoyue, Koch-Bojalad, Bailey A., Yoon, Sora, Shah, Parisha P., Karnay, Ashley, Park, Daniel S., Luppino, Jennifer M., Nguyen, Son C., Padmanabhan, Arun, Smith, Cheryl L., Poleshko, Andrey, Wang, Qiaohong, Li, Li, Srivastava, Deepak, Vahedi, Golnaz, Eom, Gwang Hyeon, Blobel, Gerd A., Joyce, Eric F., and Jain, Rajan

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results