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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 publication

DOI

10.1016/j.cell.2010.01.003

Type

Journal article

Journal

Cell

Publication Date

05/03/2010

Volume

140

Pages

678 - 691

Keywords

Animals, Binding Sites, Cell Cycle Proteins, Embryonic Stem Cells, Genome, Histone Chaperones, Histones, Mice, Mice, Inbred C57BL, Telomere, Transcription Factors, Transcription Initiation Site