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Dev Cell. 2014 Jul 14;30(1):11-22. doi: 10.1016/j.devcel.2014.05.024. Epub 2014 Jul 3.

High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm.

Author information

1
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Institute of Bioinformatics and System Biology, National Chiao Tung University, 75 Bo-Ai Street, Hsin-Chu, Taiwan 300; Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
4
Institute of Bioinformatics and System Biology, National Chiao Tung University, 75 Bo-Ai Street, Hsin-Chu, Taiwan 300.
5
Department of Developmental and Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
6
Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
7
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: oliver.rando@umassmed.edu.

Abstract

Mammalian embryonic stem cells (ESCs) and sperm exhibit unusual chromatin packaging that plays important roles in cellular function. Here, we extend a recently developed technique, based on deep paired-end sequencing of lightly digested chromatin, to assess footprints of nucleosomes and other DNA-binding proteins genome-wide in murine ESCs and sperm. In ESCs, we recover well-characterized features of chromatin such as promoter nucleosome depletion and further identify widespread footprints of sequence-specific DNA-binding proteins such as CTCF, which we validate in knockdown studies. We document global differences in nuclease accessibility between ESCs and sperm, finding that the majority of histone retention in sperm preferentially occurs in large gene-poor genomic regions, with only a small subset of nucleosomes being retained over promoters of developmental regulators. Finally, we describe evidence that CTCF remains associated with the genome in mature sperm, where it could play a role in organizing the sperm genome.

PMID:
24998598
PMCID:
PMC4184102
DOI:
10.1016/j.devcel.2014.05.024
[Indexed for MEDLINE]
Free PMC Article
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