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Nat Cell Biol. 2016 Nov;18(11):1127-1138. doi: 10.1038/ncb3424. Epub 2016 Oct 17.

Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a.

Author information

1
Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.
2
Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.
3
Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
4
Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, New York 10016, USA.
5
Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York 10016, USA.
6
Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
7
Genome Technology Center, Office of Collaborative Science, NYU School of Medicine, New York, New York 10016, USA.
8
Department of Cell Biology, NYU School of Medicine, New York, New York 10016, USA.

Abstract

Pluripotent embryonic stem cells (ESCs) self-renew or differentiate into all tissues of the developing embryo and cell-specification factors are necessary to balance gene expression. Here we delineate the function of the PHD-finger protein 5a (Phf5a) in ESC self-renewal and ascribe its role in regulating pluripotency, cellular reprogramming and myoblast specification. We demonstrate that Phf5a is essential for maintaining pluripotency, since depleted ESCs exhibit hallmarks of differentiation. Mechanistically, we attribute Phf5a function to the stabilization of the Paf1 transcriptional complex and control of RNA polymerase II elongation on pluripotency loci. Apart from an ESC-specific factor, we demonstrate that Phf5a controls differentiation of adult myoblasts. Our findings suggest a potent mode of regulation by Phf5a in stem cells, which directs their transcriptional programme, ultimately regulating maintenance of pluripotency and cellular reprogramming.

PMID:
27749823
PMCID:
PMC5083132
DOI:
10.1038/ncb3424
[Indexed for MEDLINE]
Free PMC Article

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