Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters
- Vibhor Kumar1,6,
- Nirmala Arul Rayan1,6,
- Masafumi Muratani2,3,6,
- Stefan Lim1,
- Bavani Elanggovan1,
- Lixia Xin1,
- Tess Lu1,
- Harshyaa Makhija1,
- Jeremie Poschmann1,
- Thomas Lufkin3,4,
- Huck Hui Ng3,5 and
- Shyam Prabhakar1
- 1Computational and Systems Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
- 2Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan;
- 3Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore;
- 4Department of Biology, Clarkson University, Potsdam, New York 13699, USA;
- 5Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore
- Corresponding authors: prabhakars{at}gis.a-star.edu.sg, nghh{at}gis.a-star.edu.sg
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↵6 These authors contributed equally to this work.
Abstract
Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.201038.115.
- Received October 18, 2015.
- Accepted March 7, 2016.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
