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

Alexandros Strikoudis, Charalampos Lazaris, Thomas Trimarchi, Antonio L. Galvao Neto, Yan Yang, Panagiotis Ntziachristos, Scott Rothbart, Shannon Buckley, Igor Dolgalev, Matthias Stadtfeld, Brian D. Strahl, Brian D. Dynlacht, Aristotelis Tsirigos, Iannis Aifantis

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1127-1138
Number of pages12
JournalNature Cell Biology
Volume18
Issue number11
DOIs
StatePublished - Oct 27 2016

ASJC Scopus subject areas

  • Cell Biology

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