Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions

Aaron D. Goldberg, Laura A. Banaszynski, Kyung Min Noh, Peter W. Lewis, Simon J. Elsaesser, Sonja Stadler, Scott Dewell, Martin Law, Xingyi Guo, Xuan Li, Duancheng Wen, Ariane Chapgier, Russell C. DeKelver, Jeffrey C. Miller, Ya Li Lee, Elizabeth A. Boydston, Michael C. Holmes, Philip D. Gregory, John M. Greally, Shahin RafiiChingwen Yang, Peter J. Scambler, David Garrick, Richard J. Gibbons, Douglas R. Higgs, Ileana M. Cristea, Fyodor D. Urnov, Deyou Zheng, C. David Allis

Research output: Contribution to journalArticlepeer-review

960 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)678-691
Number of pages14
Issue number5
StatePublished - Mar 5 2010

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology


  • DNA


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