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G3 (Bethesda). 2014 Aug 12;4(11):2051-63. doi: 10.1534/g3.114.013565.

Distinct and predictive histone lysine acetylation patterns at promoters, enhancers, and gene bodies.

Author information

  • 1Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653 Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, California 92037 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
  • 2Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, California 90095.
  • 3Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Richardson, Texas 75080.
  • 4Cold Spring Harbor Laboratory, 1 Bungtown Rd., Cold Spring Harbor, New York 11724 Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794.
  • 5Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Richardson, Texas 75080 Bioinformatics Division, Center for Synthetic and Systems Biology, Tsinghua National Laboratory for Information Science and Technology, Tsinghua University, Beijing 100084, China.
  • 6Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142.
  • 7Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, California 92093-0653 Department of Cellular and Molecular Medicine, Institute of Genomic Medicine, and Moores Cancer Center, University of California, San Diego School of Medicine, La Jolla, California 92093 biren@ucsd.edu.

Abstract

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.

Copyright © 2014 Rajagopal et al.

KEYWORDS:

enhancers; gene bodies; histone lysine acetylations; promoters; splicing

PMID:
25122670
[PubMed - in process]
PMCID:
PMC4232531
Free PMC Article
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