School of Natural Sciences and Mathematics
Permanent URI for this communityhttps://hdl.handle.net/10735.1/1347
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Browsing School of Natural Sciences and Mathematics by Subject "Acetylation"
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Item Distinct and Predictive Histone Lysine Acetylation Patterns at Promoters, Enhancers, and Gene Bodies(Genetics Society America, 2014-11-01) Rajagopal, Nisha; Ernst, Jason; Ray, Pradipta; Wu, Jie; Zhang, Michael Q.; Kellis, Manolis; Ren, Bing; 0000 0001 1707 1372 (Zhang, MQ); 99086074 (Zhang, MQ); Zhang, Michael Q.In eukaryotic cells, histone lysines are frequently acetylated. However, unlike modifications such as methylations, histone acetylation modifications are often considered redundant. As such, the functional roles of distinct histone acetylations are largely unexplored. We previously developed an algorithm RFECS to discover the most informative modifications associated with the classification or prediction of mammalian enhancers. Here, we used this tool to identify the modifications most predictive of promoters, enhancers, and gene bodies. Unexpectedly, we found that histone acetylation alone performs well in distinguishing these unique genomic regions. Further, we found the association of characteristic acetylation patterns with genic regions and association of chromatin state with splicing. Taken together, our work underscores the diverse functional roles of histone acetylation in gene regulation and provides several testable hypotheses to dissect these roles.Item Histone Deacetylases Positively Regulate Transcription Through the Elongation Machinery(Elsevier B.V., 2015-11-17) Greer, Celeste B.; Tanaka, Yoshiaki; Kim, Yoon Jung; Xie, Peng; Zhang, Michael Q.; Park, In-Hyun; Kim, Tae Hoon; 0000 0001 1707 1372 (Zhang, MQ); Kim, Yoon Jung; Xie, Peng; Zhang, Michael Q.; Park, In-HyunTranscription elongation regulates the expression of many genes, including oncogenes. Histone deacetylase (HDAC) inhibitors (HDACIs) block elongation, suggesting that HDACs are involved in gene activation. To understand this, we analyzed nascent transcription and elongation factor binding genome-wide after perturbation of elongation with small molecule inhibitors. We found that HDACI-mediated repression requires heat shock protein 90 (HSP90) activity. HDACIs promote the association of RNA polymerase II (RNAP2) and negative elongation factor (NELF), a complex stabilized by HSP90, at the same genomic sites. Additionally, HDACIs redistribute bromodomain-containing protein 4 (BRD4), a key elongation factor involved in enhancer activity. BRD4 binds to newly acetylated sites, and its occupancy at promoters and enhancers is reduced. Furthermore, HDACIs reduce enhancer activity, as measured by enhancer RNA production. Therefore, HDACs are required for limiting acetylation in gene bodies and intergenic regions. This facilitates the binding of elongation factors to properly acetylated promoters and enhancers for efficient elongation.; Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.