p21 transcription is regulated by differential localization of histone H2A.Z

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...

Full description

Saved in:
Bibliographic Details
Published in:Genes & development 2007-08, Vol.21 (15), p.1869-1881
Main Authors: Gévry, Nicolas, Chan, Ho Man, Laflamme, Liette, Livingston, David M, Gaudreau, Luc
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Base Sequence
Binding Sites - genetics
Cell Line
Cells, Cultured
Cellular Senescence
Chromatin - genetics
Chromatin - metabolism
Cyclin-Dependent Kinase Inhibitor p21 - genetics
DNA Damage
DNA Helicases - genetics
DNA Helicases - metabolism
DNA, Complementary - genetics
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Epigenesis, Genetic
Fibroblasts - cytology
Fibroblasts - metabolism
Histone Acetyltransferases - metabolism
Histones - metabolism
Humans
Lysine Acetyltransferase 5
Molecular Sequence Data
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myc - metabolism
Research Paper
Transcription, Genetic
Tumor Suppressor Protein p53 - deficiency
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1545707