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 journalArticle

676 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)678-691
Number of pages14
JournalCell
Volume140
Issue number5
DOIs
StatePublished - Mar 5 2010

Fingerprint

Telomere
Histones
Genes
Genome
Zinc Fingers
Embryonic Stem Cells
Epigenomics
Amino Acid Sequence
Mass Spectrometry
Transcription Factors
Binding Sites
RNA
Stem cells
Purification
Mass spectrometry
Zinc
Proteins
Cells
Data storage equipment
Amino Acids

Keywords

  • DNA
  • PROTEINS
  • STEMCELL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Goldberg, A. D., Banaszynski, L. A., Noh, K. M., Lewis, P. W., Elsaesser, S. J., Stadler, S., ... Allis, C. D. (2010). Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions. Cell, 140(5), 678-691. https://doi.org/10.1016/j.cell.2010.01.003

Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions. / Goldberg, Aaron D.; Banaszynski, Laura A.; Noh, Kyung Min; Lewis, Peter W.; Elsaesser, Simon J.; Stadler, Sonja; Dewell, Scott; Law, Martin; Guo, Xingyi; Li, Xuan; Wen, Duancheng; Chapgier, Ariane; DeKelver, Russell C.; Miller, Jeffrey C.; Lee, Ya Li; Boydston, Elizabeth A.; Holmes, Michael C.; Gregory, Philip D.; Greally, John M.; Rafii, Shahin; Yang, Chingwen; Scambler, Peter J.; Garrick, David; Gibbons, Richard J.; Higgs, Douglas R.; Cristea, Ileana M.; Urnov, Fyodor D.; Zheng, Deyou; Allis, C. David.

In: Cell, Vol. 140, No. 5, 05.03.2010, p. 678-691.

Research output: Contribution to journalArticle

Goldberg, AD, Banaszynski, LA, Noh, KM, Lewis, PW, Elsaesser, SJ, Stadler, S, Dewell, S, Law, M, Guo, X, Li, X, Wen, D, Chapgier, A, DeKelver, RC, Miller, JC, Lee, YL, Boydston, EA, Holmes, MC, Gregory, PD, Greally, JM, Rafii, S, Yang, C, Scambler, PJ, Garrick, D, Gibbons, RJ, Higgs, DR, Cristea, IM, Urnov, FD, Zheng, D & Allis, CD 2010, 'Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions', Cell, vol. 140, no. 5, pp. 678-691. https://doi.org/10.1016/j.cell.2010.01.003
Goldberg AD, Banaszynski LA, Noh KM, Lewis PW, Elsaesser SJ, Stadler S et al. Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions. Cell. 2010 Mar 5;140(5):678-691. https://doi.org/10.1016/j.cell.2010.01.003
Goldberg, Aaron D. ; Banaszynski, Laura A. ; Noh, Kyung Min ; Lewis, Peter W. ; Elsaesser, Simon J. ; Stadler, Sonja ; Dewell, Scott ; Law, Martin ; Guo, Xingyi ; Li, Xuan ; Wen, Duancheng ; Chapgier, Ariane ; DeKelver, Russell C. ; Miller, Jeffrey C. ; Lee, Ya Li ; Boydston, Elizabeth A. ; Holmes, Michael C. ; Gregory, Philip D. ; Greally, John M. ; Rafii, Shahin ; Yang, Chingwen ; Scambler, Peter J. ; Garrick, David ; Gibbons, Richard J. ; Higgs, Douglas R. ; Cristea, Ileana M. ; Urnov, Fyodor D. ; Zheng, Deyou ; Allis, C. David. / Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions. In: Cell. 2010 ; Vol. 140, No. 5. pp. 678-691.
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