Transient Pairing of Homologous Oct4 Alleles Accompanies the Onset of Embryonic Stem Cell Differentiation

Hogan, Megan S, Parfitt, David-Emlyn, Zepeda-Mendoza, Cinthya J, Shen, Michael M, Spector, David L (2015) Transient Pairing of Homologous Oct4 Alleles Accompanies the Onset of Embryonic Stem Cell Differentiation. Cell Stem Cell, 16 (3). pp. 275-288. ISSN 1934-5909

URL: http://www.ncbi.nlm.nih.gov/pubmed/25748933
DOI: 10.1016/j.stem.2015.02.001

Abstract

Summary The relationship between chromatin organization and transcriptional regulation is an area of intense investigation. We characterized the spatial relationships between alleles of the Oct4, Sox2, and Nanog genes in single cells during the earliest stages of mouse embryonic stem cell (ESC) differentiation and during embryonic development. We describe homologous pairing of the Oct4 alleles during ESC differentiation and embryogenesis, and we present evidence that pairing is correlated with the kinetics of ESC differentiation. Importantly, we identify critical DNA elements within the Oct4 promoter/enhancer region that mediate pairing of Oct4 alleles. Finally, we show that mutation of OCT4/SOX2 binding sites within this region abolishes inter-chromosomal interactions and affects accumulation of the repressive H3K9me2 modification at the Oct4 enhancer. Our findings demonstrate that chromatin organization and transcriptional programs are intimately connected in ESCs and that the dynamic positioning of the Oct4 alleles is associated with the transition from pluripotency to lineage specification.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Oct4
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Sox2
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Spector lab
Watson School > Publications
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Highlight: Spector, David L.
Depositing User: Matt Covey
Date Deposited: 13 Mar 2015 13:31
Last Modified: 03 Oct 2016 14:59
PMCID: PMC4355581
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31267

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