title: Distinct factors control histone variant H3.3 localization at specific genomic regions.
abstract: The incorporation of histone H3 variants has been implicated in the epigenetic memory of cellular state. Using genome editing with zinc-finger nucleases to tag endogenous H3.3, we report genome-wide profiles of H3 variants in mammalian embryonic stem cells and neuronal precursor cells. Genome-wide patterns of H3.3 are dependent on amino acid sequence and change with cellular differentiation at developmentally regulated loci. The H3.3 chaperone Hira is required for H3.3 enrichment at active and repressed genes. Strikingly, Hira is not essential for localization of H3.3 at telomeres and many transcription factor binding sites. Immunoaffinity purification and mass spectrometry reveal that the proteins Atrx and Daxx associate with H3.3 in a Hira-independent manner. Atrx is required for Hira-independent localization of H3.3 at telomeres and for the repression of telomeric RNA. Our data demonstrate that multiple and distinct factors are responsible for H3.3 localization at specific genomic locations in mammalian cells.
authors.affiliation: Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Goldberg
authors.forename: Laura A
authors.initials: LA
authors.lastname: Banaszynski
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Noh
authors.forename: Peter W
authors.initials: PW
authors.lastname: Lewis
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Elsaesser
authors.forename: Sonja
authors.initials: S
authors.lastname: Stadler
authors.forename: Scott
authors.initials: S
authors.lastname: Dewell
authors.forename: Martin
authors.initials: M
authors.lastname: Law
authors.forename: Xingyi
authors.initials: X
authors.lastname: Guo
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Duancheng
authors.initials: D
authors.lastname: Wen
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Russell C
authors.initials: RC
authors.lastname: DeKelver
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Miller
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Lee
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Boydston
authors.forename: Michael C
authors.initials: MC
authors.lastname: Holmes
authors.forename: Philip D
authors.initials: PD
authors.lastname: Gregory
authors.forename: John M
authors.initials: JM
authors.lastname: Greally
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.forename: Chingwen
authors.initials: C
authors.lastname: Yang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scambler
authors.forename: David
authors.initials: D
authors.lastname: Garrick
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gibbons
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Higgs
authors.forename: Ileana M
authors.initials: IM
authors.lastname: Cristea
authors.forename: Fyodor D
authors.initials: FD
authors.lastname: Urnov
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
mesh_terms: D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000378:metabolism; D016678:Genome; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D018797:Cell Cycle Proteins; C484187:Hira protein, mouse; D056488:Histone Chaperones; D006657:Histones; D014157:Transcription Factors