@article{ff50ef8024d741b8988a2e32490abe93,
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.",
keywords = "DNA, PROTEINS, STEMCELL",
author = "Goldberg, {Aaron D.} and Banaszynski, {Laura A.} and Noh, {Kyung Min} and Lewis, {Peter W.} and Elsaesser, {Simon J.} and Sonja Stadler and Scott Dewell and Martin Law and Xingyi Guo and Xuan Li and Duancheng Wen and Ariane Chapgier and DeKelver, {Russell C.} and Miller, {Jeffrey C.} and Lee, {Ya Li} and Boydston, {Elizabeth A.} and Holmes, {Michael C.} and Gregory, {Philip D.} and Greally, {John M.} and Shahin Rafii and Chingwen Yang and Scambler, {Peter J.} and David Garrick and Gibbons, {Richard J.} and Higgs, {Douglas R.} and Cristea, {Ileana M.} and Urnov, {Fyodor D.} and Deyou Zheng and Allis, {C. David}",
note = "Funding Information: We thank L. Baker, E.M. Duncan, G.G. Wang for critical reading of the manuscript, P. Wu, A. Sfeir, and T. de Lange for telomere reagents and helpful discussion, P.D. Adams for Hira antibodies, R. Jaenisch for F1 hybrid male 129SVJae × M. m. castaneus ESCs, G. Almouzni for H3.1 and H3.3-FLAG-HA HeLa cells, K. Zhao for sharing his native ChIP-seq protocol, E. Moehle for drawing the gene editing schemes, N. Jina of the University College London Genomics Core, K.R. Molloy for assistance with mass spectrometric analysis, and S. Mazel and A. North of the Rockefeller University Flow Cytometry and Bio-Imaging Resource Centers. A.D.G. is supported by National Institutes of Health (NIH) Medical Scientist Training Program grant GM07739. L.A.B. is a Damon Runyon Cancer Research Foundation fellow. This work was funded by institutional support from The Rockefeller University and grants from the Tri-Institutional Stem Cell Initiative (funded by the Starr Foundation), Empire State Stem Cell fund through New York State Department of Health contract #C023046, the Howard Hughes Medical Institute (S.R.), Biotechnology and Biological Sciences Research Council UK and the British Heart Foundation (P.J.S.), startup funds from the Albert Einstein College of Medicine of Yeshiva University (D.Z.), and NIH grants RR00862, RR022220, DP1DA026192 (I.M.C.), GM53122, and GM53512 (C.D.A.). J.C.M., M.C.H., Y.L.L., P.D.G., and F.D.U. are full-time employees of Sangamo BioSciences, Inc. ",
year = "2010",
month = mar,
day = "5",
doi = "10.1016/j.cell.2010.01.003",
language = "English (US)",
volume = "140",
pages = "678--691",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",
}