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

Goldberg, AD; Banaszynski, LA; Noh, KM; Lewis, PW; Elsaesser, SJ; Stadler, S; Dewell, S; ... Allis, CD; + view all (2010) Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions. CELL , 140 (5) 678 - 691. 10.1016/j.cell.2010.01.003.

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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.

Type: Article
Title: Distinct Factors Control Histone Variant H3.3 Localization at Specific Genomic Regions
DOI: 10.1016/j.cell.2010.01.003
Keywords: ZINC-FINGER NUCLEASES, EMBRYONIC STEM-CELLS, REPEAT-CONTAINING RNA, ATR-X SYNDROME, MAMMALIAN TELOMERES, SYNDROME PROTEIN, GENE-EXPRESSION, POLYMERASE-II, DNA-SYNTHESIS, ES CELLS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Development Bio and Cancer Prog
URI: http://discovery.ucl.ac.uk/id/eprint/135403
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