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 M Buckley-McKeown, Igor Dolgalev, Matthias Stadtfeld, Brian D. Strahl, Brian D. Dynlacht, Aristotelis Tsirigos, Iannis Aifantis

Research output: Contribution to journalArticle

15 Citations (Scopus)

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

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Fingers
Cell Differentiation
Embryonic Stem Cells
Myoblasts
Proteins
Pluripotent Stem Cells
Stem Cell Factor
RNA Polymerase II
Stem Cells
Embryonic Structures
Maintenance
Gene Expression
Cellular Reprogramming

ASJC Scopus subject areas

  • Cell Biology

Cite this

Strikoudis, A., Lazaris, C., Trimarchi, T., Galvao Neto, A. L., Yang, Y., Ntziachristos, P., ... Aifantis, I. (2016). Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a. Nature Cell Biology, 18(11), 1127-1138. https://doi.org/10.1038/ncb3424

Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a. / Strikoudis, Alexandros; Lazaris, Charalampos; Trimarchi, Thomas; Galvao Neto, Antonio L.; Yang, Yan; Ntziachristos, Panagiotis; Rothbart, Scott; Buckley-McKeown, Shannon M; Dolgalev, Igor; Stadtfeld, Matthias; Strahl, Brian D.; Dynlacht, Brian D.; Tsirigos, Aristotelis; Aifantis, Iannis.

In: Nature Cell Biology, Vol. 18, No. 11, 27.10.2016, p. 1127-1138.

Research output: Contribution to journalArticle

Strikoudis, A, Lazaris, C, Trimarchi, T, Galvao Neto, AL, Yang, Y, Ntziachristos, P, Rothbart, S, Buckley-McKeown, SM, Dolgalev, I, Stadtfeld, M, Strahl, BD, Dynlacht, BD, Tsirigos, A & Aifantis, I 2016, 'Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a', Nature Cell Biology, vol. 18, no. 11, pp. 1127-1138. https://doi.org/10.1038/ncb3424
Strikoudis A, Lazaris C, Trimarchi T, Galvao Neto AL, Yang Y, Ntziachristos P et al. Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a. Nature Cell Biology. 2016 Oct 27;18(11):1127-1138. https://doi.org/10.1038/ncb3424
Strikoudis, Alexandros ; Lazaris, Charalampos ; Trimarchi, Thomas ; Galvao Neto, Antonio L. ; Yang, Yan ; Ntziachristos, Panagiotis ; Rothbart, Scott ; Buckley-McKeown, Shannon M ; Dolgalev, Igor ; Stadtfeld, Matthias ; Strahl, Brian D. ; Dynlacht, Brian D. ; Tsirigos, Aristotelis ; Aifantis, Iannis. / Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a. In: Nature Cell Biology. 2016 ; Vol. 18, No. 11. pp. 1127-1138.
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