title: Distinct and predictive histone lysine acetylation patterns at promoters, enhancers, and gene bodies.
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.
authors.affiliation: Ludwig 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.
authors.forename: Nisha
authors.initials: N
authors.lastname: Rajagopal
authors.affiliation: Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, California 90095.
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.affiliation: Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Richardson, Texas 75080.
authors.forename: Pradipta
authors.initials: P
authors.lastname: Ray
authors.affiliation: Cold 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.affiliation: Ludwig 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.
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
mesh_terms: D000107:Acetylation; D000465:Algorithms; D017398:Alternative Splicing; D000818:Animals; D002843:Chromatin / Q000235:genetics; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D002843:Chromatin; D006657:Histones
keywords: enhancers; gene bodies; histone lysine acetylations; promoters; splicing