p21 transcription is regulated by differential localization of histone H2A.Z (original) (raw)

  1. Nicolas Gévry1,3,
  2. Ho Man Chan2,3,
  3. Liette Laflamme1,
  4. David M. Livingston2,5, and
  5. Luc Gaudreau1,4
  6. 1 Département de biologie, Faculté des sciences, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada;
  7. 2 Dana-Farber Cancer Institute Harvard Medical School, Boston, Massachusetts 02115, USA
  8. ↵3 These authors contributed equally to this work.

Abstract

In yeast cells, H2A.Z regulates transcription and is globally associated within a few nucleosomes of the initiator regions of numerous promoters. H2A.Z is deposited at these loci by an ATP-dependent complex, Swr1.com. Here we show that H2A.Z suppresses the p53 → p21 transcription and senescence responses. Upon DNA damage, H2A.Z is first evicted from the p21 promoter, followed by the recruitment of the Tip60 histone acetyltransferase to activate p21 transcription. p400, a human Swr1 homolog, is required for the localization of H2A.Z, and largely colocalizes with H2A.Z at multiple promoters investigated. Notably, the presence of sequence-specific transcription factors, such as p53 and Myc, provides positioning cues that direct the location of H2A.Z-containing nucleosomes within these promoters. Collectively, this study strongly suggests that certain sequence-specific transcription factors regulate transcription, in part, by preferentially positioning histone variant H2A.Z within chromatin. This H2A.Z-centered process is part of an epigenetic process for modulating gene expression.

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