2005
DOI: 10.1038/ncb1235
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Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin

Abstract: Here, we show a role for the RB1 family proteins in directing full heterochromatin formation. Mouse embryonic fibroblasts that are triply deficient for RB1 (retinoblastoma 1), RBL1 (retinoblastoma-like 1) and RBL2 (retinoblastoma-like 2) - known as TKO cells - show a marked genomic instability, which is coincidental with decreased DNA methylation, increased acetylation of histone H3 and decreased tri-methylation of histone H4 at lysine 20 (H4K20). Chromatin immunoprecipitation showed that H4K20 tri-methylation… Show more

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Cited by 318 publications
(322 citation statements)
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“…Through an interaction with the E2F transcription factor, the pRB protein facilitates formation of heterochromatin at E2F target genes and other sites throughout the genome (48,147). For example, pRB recruits the histone methylase Suv39h1 to chromatin and, as described above, this enzyme is required for oncogene-induced formation of heterochromatin in murine T-cells (16).…”
Section: Relationship Of Sahf Assembly To the Prb And P53 Tumor Supprmentioning
confidence: 95%
“…Through an interaction with the E2F transcription factor, the pRB protein facilitates formation of heterochromatin at E2F target genes and other sites throughout the genome (48,147). For example, pRB recruits the histone methylase Suv39h1 to chromatin and, as described above, this enzyme is required for oncogene-induced formation of heterochromatin in murine T-cells (16).…”
Section: Relationship Of Sahf Assembly To the Prb And P53 Tumor Supprmentioning
confidence: 95%
“…Interestingly, our data reveal that loss of SNF5, another core subunit of the SWI/SNF complex, does not elicit dissolution of heterochromatin domains, nor does it affect the localization of trimethylation on histone H4 lysine 20 or histone H3 lysine 9 (Supplemental Figure S2). It is well established that these histone markers are not required for the structural maintenance of the heterochromatin domains, because deletion of Suv39H1/H2 and retinoblastoma (RB)-related family members results in the loss of trimethylation of histone H3 lysine 9 and histone H4 lysine 20 at heterochromatin domains, respectively, without compromising the integrity of the overall chromatin domain structure (Peters et al, 2001;Gonzalo et al, 2005). Thus, the maintenance of pericentromeric heterochromatin domains is hierarchical, with an underlying Brg1-dependent function that is critical for structural integrity.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to binding E2F-1 and preventing its transcriptional activity, pRb can also actively repress transcription through targeting chromatin-remodelling enzymes, such as histone deacetylases and methyltransferases, and interact with chromatin-associated proteins to influence the chromatin environment (Longworth and Dyson, 2010). The observation that pRb interacts with a wide range of chromatin-binding proteins and chromatin-modifying enzymes has led to the concept that pRb can exert global control upon chromatin, a notion which is strengthened by the fact that cells lacking pRb family members display altered chromatin states and exhibit chromosomal aberrations (Herrera et al, 1996;Gonzalo et al, 2005).…”
Section: Introductionmentioning
confidence: 99%