The histone demethylase Jarid1b (Kdm5b) is a novel component of the Rb pathway and associates with E2f-target genes in MEFs during senescence.
The histone demethylase Jarid1b (Kdm5b) is a novel component of the Rb pathway and associates with E2f-target genes in MEFs during senescence.
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DOI：
10.1371/journal.pone.0025235
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Beijersbergen RL
中科院分区：
文献类型：
--
作者：
Nijwening JH;Geutjes EJ;Bernards R;Beijersbergen RL
衰老是由P53和RB途径控制的强大细胞周期停滞，它是肿瘤发生的重要障碍。衰老与基因表达的深刻改变有关，包括通过异染色质形成对E2F靶向基因的稳定抑制。染色质组合物中的一些变化是由RB策划的。与E2F复杂，RB募集染色质将酶修改为E2F靶基因，从而导致其转录抑制。为了鉴定特异性在RB途径中发挥作用的新型染色质重塑酶，我们使用了功能性遗传筛选模型来绕过鼠细胞中的衰老。我们将H3K4-甲基酶JARID1B鉴定为此筛选模型中RB途径的新成分。我们发现在细胞衰老期间，RB1的JARID1B表型敲低的耗尽，JARID1B与E2F靶向基因相关。这些结果表明JARID1b在衰老过程中对细胞周期基因的抑制作用中的作用。
Senescence is a robust cell cycle arrest controlled by the p53 and Rb pathways that acts as an important barrier to tumorigenesis. Senescence is associated with profound alterations in gene expression, including stable suppression of E2f-target genes by heterochromatin formation. Some of these changes in chromatin composition are orchestrated by Rb. In complex with E2f, Rb recruits chromatin modifying enzymes to E2f target genes, leading to their transcriptional repression. To identify novel chromatin remodeling enzymes that specifically function in the Rb pathway, we used a functional genetic screening model for bypass of senescence in murine cells. We identified the H3K4-demethylase Jarid1b as novel component of the Rb pathway in this screening model. We find that depletion of Jarid1b phenocopies knockdown of Rb1 and that Jarid1b associates with E2f-target genes during cellular senescence. These results suggest a role for Jarid1b in Rb-mediated repression of cell cycle genes during senescence.
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