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

doi:10.1038/ncb3424

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^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

39 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 language	English (US)
Pages (from-to)	1127-1138
Number of pages	12
Journal	Nature Cell Biology
Volume	18
Issue number	11
DOIs	https://doi.org/10.1038/ncb3424
State	Published - Oct 27 2016

ASJC Scopus subject areas

Cell Biology

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Strikoudis, A., Lazaris, C., Trimarchi, T., Galvao Neto, A. L., Yang, Y., Ntziachristos, P., Rothbart, S., Buckley, S., Dolgalev, I., Stadtfeld, M., Strahl, B. D., Dynlacht, B. D., Tsirigos, A., & 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

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

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.",

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

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Strikoudis, A, Lazaris, C, Trimarchi, T, Galvao Neto, AL, Yang, Y, Ntziachristos, P, Rothbart, S, Buckley, S, 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

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AU - Lazaris, Charalampos

AU - Trimarchi, Thomas

AU - Galvao Neto, Antonio L.

AU - Yang, Yan

AU - Ntziachristos, Panagiotis

AU - Rothbart, Scott

AU - Buckley, Shannon

AU - Dolgalev, Igor

AU - Stadtfeld, Matthias

AU - Strahl, Brian D.

AU - Dynlacht, Brian D.

AU - Tsirigos, Aristotelis

AU - Aifantis, Iannis

PY - 2016/10/27

Y1 - 2016/10/27

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

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