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.
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Strikoudis
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.|Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Charalampos
authors.identifier: http://orcid.org/0000-0002-7345-8288
authors.initials: C
authors.lastname: Lazaris
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Trimarchi
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Ronald O. Perelman Department of Dermatology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Galvao Neto
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Ntziachristos
authors.affiliation: Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Rothbart
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Buckley
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.|Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, New York 10016, USA.|Genome Technology Center, Office of Collaborative Science, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Igor
authors.identifier: http://orcid.org/0000-0003-4451-126X
authors.initials: I
authors.lastname: Dolgalev
authors.affiliation: Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.|Department of Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stadtfeld
authors.affiliation: Department of Biochemistry and Biophysics and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Dynlacht
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Center for Health Informatics and Bioinformatics, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Tsirigos
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, New York 10016, USA.|Laura &Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, New York 10016, USA.|Helen L. &Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Iannis
authors.initials: I
authors.lastname: Aifantis
mesh_terms: D000375:Aging; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D004268:DNA-Binding Proteins; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology*; D039904:Pluripotent Stem Cells / Q000166:cytology*; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C459458:Phf5a protein, mouse; D016601:RNA-Binding Proteins; D015534:Trans-Activators