Genome-Wide Studies Reveal that H3K4me3 Modification in Bivalent Genes Is Dynamically Regulated during the Pluripotent Cell Cycle and Stabilized upon Differentiation.

Autor:	Grandy RA; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA., Whitfield TW; Department of Cell and Developmental Biology and Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts, USA., Wu H; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA., Fitzgerald MP; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA., VanOudenhove JJ; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA., Zaidi SK; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA., Montecino MA; Center for Biomedical Research and FONDAP Center for Genome Regulation, Universidad Andres Bello, Santiago, Chile., Lian JB; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA., van Wijnen AJ; Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA., Stein JL; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA., Stein GS; Department of Biochemistry and University of Vermont Cancer Center, University of Vermont College of Medicine, Burlington, Vermont, USA gary.stein@uvm.edu.
Jazyk:	angličtina
Zdroj:	Molecular and cellular biology [Mol Cell Biol] 2015 Dec 07; Vol. 36 (4), pp. 615-27. Date of Electronic Publication: 2015 Dec 07 (Print Publication: 2016).
DOI:	10.1128/MCB.00877-15
Abstrakt:	Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotency. (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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