DOI: 10.1101/gad.1499407. pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16<i><sup>INK4a</sup></i> tumor suppressor gene

pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4a tumor suppressor gene

10.1101/gad.1499407

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Genetic studies have demonstrated that Bmi1 promotes cell proliferation and stem cell self-renewal with a correlative decrease of p16INK4a expression. Here, we demonstrate that Polycomb genes EZH2 and BMI1 repress p16 expression in human and mouse primary cells, but not in cells deficient for pRB protein function. The p16 locus is H3K27-methylated and bound by BMI1, RING2, and SUZ12. Inactivation of pRB family proteins abolishes H3K27 methylation and disrupts BMI1, RING2, and SUZ12 binding to the p16 locus. These results suggest a model in which pRB proteins recruit PRC2 to trimethylate p16, priming the BMI1-containing PRC1L ubiquitin ligase complex to silence p16.

Authors 6

Yojiro Kotake (first)
Ru Cao (additional)
Patrick Viatour (additional)
Julien Sage (additional)
Yi Zhang (additional)
Yue Xiong (additional)

References 24 Referenced 263

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{'key': '2021111607465838000_21.1.49.10', 'first-page': '6078', 'article-title': 'Transcriptional repression of the D-type cyclin-dependent kinases inhibitor p16 by the retinoblastoma susceptibility gene product, pRb', 'volume': '54', 'author': 'Li,', 'year': '1994', 'journal-title': 'Cancer Res.'} / Cancer Res. / Transcriptional repression of the D-type cyclin-dependent kinases inhibitor p16 by the retinoblastoma susceptibility gene product, pRb by Li, (1994)
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{'key': '2021111607465838000_21.1.49.18', 'first-page': '5816', 'article-title': 'Differential expression and cell cycle regulation of the cyclin-dependent kinase 4 p16Ink4', 'volume': '54', 'author': 'Tam,', 'year': '1994', 'journal-title': 'Cancer Res.'} / Cancer Res. / Differential expression and cell cycle regulation of the cyclin-dependent kinase 4 p16Ink4 by Tam, (1994)
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Dates

Type	When
Created	18 years, 7 months ago (Jan. 8, 2007, 2:57 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 12:02 p.m.)
Indexed	21 hours, 14 minutes ago (Sept. 3, 2025, 6:05 a.m.)
Issued	18 years, 8 months ago (Jan. 1, 2007)
Published	18 years, 8 months ago (Jan. 1, 2007)
Published Online	18 years, 7 months ago (Jan. 8, 2007)
Published Print	18 years, 8 months ago (Jan. 1, 2007)

Funders 0

None

BibTeX

@article{Kotake_2007, title={pRB family proteins are required for H3K27 trimethylation and Polycomb repression complexes binding to and silencing p16INK4a tumor suppressor gene}, volume={21}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1499407}, DOI={10.1101/gad.1499407}, number={1}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Kotake, Yojiro and Cao, Ru and Viatour, Patrick and Sage, Julien and Zhang, Yi and Xiong, Yue}, year={2007}, month=jan, pages={49–54} }

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