Distinct factors control histone variant H3.3 localization at specific genomic regions.
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.
Goldberg
Aaron D
AD
Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Banaszynski
Laura A
LA
Noh
Kyung-Min
KM
Lewis
Peter W
PW
Elsaesser
Simon J
SJ
Stadler
Sonja
S
Dewell
Scott
S
Law
Martin
M
Guo
Xingyi
X
Li
Xuan
X
Wen
Duancheng
D
Chapgier
Ariane
A
DeKelver
Russell C
RC
Miller
Jeffrey C
JC
Lee
Ya-Li
YL
Boydston
Elizabeth A
EA
Holmes
Michael C
MC
Gregory
Philip D
PD
Greally
John M
JM
Rafii
Shahin
S
Yang
Chingwen
C
Scambler
Peter J
PJ
Garrick
David
D
Gibbons
Richard J
RJ
Higgs
Douglas R
DR
Cristea
Ileana M
IM
Urnov
Fyodor D
FD
Zheng
Deyou
D
Allis
C David
CD
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
D018797:Cell Cycle Proteins; C484187:Hira protein, mouse; D056488:Histone Chaperones; D006657:Histones; D014157:Transcription Factors