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GENES & DEVELOPMENT 21:1869-1881, 2007
©2007 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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p21 transcription is regulated by differential localization of histone H2A.Z

Nicolas Gévry1,3, Ho Man Chan2,3, Liette Laflamme1, David M. Livingston2,5, and Luc Gaudreau1,4

1 Département de biologie, Faculté des sciences, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada; 2 Dana-Farber Cancer Institute Harvard Medical School, Boston, Massachusetts 02115, USA

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.

[Keywords: H2A.Z; Myc; p21; p400; p53]

Received February 23, 2007; revised version accepted June 14, 2007.

3 These authors contributed equally to this work.

4 Corresponding authors.

E-MAIL Luc.Gaudreau{at}USherbrooke.ca; FAX (819) 821-8049.

5 E-MAIL David_Livingston{at}dfci.harvard.edu; FAX (617) 632-4381.

Supplemental material is availabe at http://www.genesdev.org.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1545707


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[Abstract] [Full Text] [PDF]


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