Publication Date:
2016-05-07
Description:
Different combinations of histone modifications have been proposed to signal distinct gene regulatory functions, but this area is poorly addressed by existing technologies. We applied high-throughput single-molecule imaging to decode combinatorial modifications on millions of individual nucleosomes from pluripotent stem cells and lineage-committed cells. We identified definitively bivalent nucleosomes with concomitant repressive and activating marks, as well as other combinatorial modification states whose prevalence varies with developmental potency. We showed that genetic and chemical perturbations of chromatin enzymes preferentially affect nucleosomes harboring specific modification states. Last, we combined this proteomic platform with single-molecule DNA sequencing technology to simultaneously determine the modification states and genomic positions of individual nucleosomes. This single-molecule technology has the potential to address fundamental questions in chromatin biology and epigenetic regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shema, Efrat -- Jones, Daniel -- Shoresh, Noam -- Donohue, Laura -- Ram, Oren -- Bernstein, Bradley E -- R44HG005279/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 May 6;352(6286):717-21. doi: 10.1126/science.aad7701.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; SeqLL, Woburn, MA 01801, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. ; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. bernstein.bradley@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27151869" target="_blank"〉PubMed〈/a〉
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
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Chemistry and Pharmacology
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Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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