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Mol Cell. 2015 Jun 18;58(6):1113-23. doi: 10.1016/j.molcel.2015.03.030. Epub 2015 May 7.

The Histone Chaperones FACT and Spt6 Restrict H2A.Z from Intragenic Locations.

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Institut de recherches cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, 373 Plantation Street, Worcester, MA 01605, USA.
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.
Institut de recherches cliniques de Montréal, 110 Avenue des Pins Ouest, Montréal, QC H2W 1R7, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, 2900 Boulevard Edouard-Montpetit, Montréal, QC H3T 1J4, Canada. Electronic address:


H2A.Z is a highly conserved histone variant involved in several key nuclear processes. It is incorporated into promoters by SWR-C-related chromatin remodeling complexes, but whether it is also actively excluded from non-promoter regions is not clear. Here we provide genomic and biochemical evidence that the RNA polymerase II (RNA Pol II) elongation-associated histone chaperones FACT and Spt6 both contribute to restricting H2A.Z from intragenic regions. In the absence of FACT or Spt6, the lack of efficient nucleosome reassembly coupled to pervasive incorporation of H2A.Z by mislocalized SWR-C alters chromatin composition and contributes to cryptic initiation. Therefore, chaperone-mediated H2A.Z confinement is crucial for restricting the chromatin signature of gene promoters that otherwise may license or promote cryptic transcription.

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