Cell cycle-dependent recruitment of HDAC-1 correlates with deacetylation of histone H4 on an Rb-E2F target promoter.
The transcription factor E2F, which is a key element in the control of cell proliferation, is repressed by Rb and other pocket proteins in growth-arrested differentiating cells, as well as in proliferating cells when they progress through early G1. It is not known whether similar mechanisms are operative in the two situations. A body of data suggests that E2F repression by pocket proteins involves class I histone deacetylases (HDACs). It has been hypothesized that these enzymes are recruited to E2F target promoters where they deacetylate histones. Here we have tested this hypothesis directly by using formaldehyde cross-linked chromatin immunoprecipitation (XChIP) assays to evaluate HDAC association in living cells. Our data show that a histone deacetylase, HDAC-1, is stably bound to an E2F target promoter during early G1 in proliferating cells and released at the G1-S transition. In addition, our results reveal an inverse correlation between HDAC-1 recruitment and histone H4 acetylation on specific lysines.
Ferreira
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Laboratoire 'Oncogenèse, Différenciation et Transduction du Signal', CNRS UPR 9079, Institut Fédératif André Lwoff, 7 rue Guy Moquet, 94801 Villejuif, France.
Naguibneva
I
I
Mathieu
M
M
Ait-Si-Ali
S
S
Robin
P
P
Pritchard
L L
LL
Harel-Bellan
A
A
D016475:3T3 Cells; D000107:Acetylation; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D002455:Cell Division; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry; D051379:Mice; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*
D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D006657:Histones; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D008239:Lysine