Association of mammalian PcG multimeric protein complexes to Hoxb8 gene

哺乳动物 PcG 多聚蛋白复合物与 Hoxb8 基因的关联

• 批准号: 14370041
• 负责人: KOSEKI Haruhiko
• 金额: $ 8.9万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370041/
• 关键词: Mouse; Polycomb; Rnf2; Ring1; Mph2; Edr1; Hox; Histon H3; Edr1; Topors; p53; Mph2; DNAダメージ

To address molecular mechanisms underlying Polycomb group (PcG) -mediated repression of Hox gene expression, we have focused on how PcG proteins, Rnf2 (Ring1B), Edr1 (Rae28/Mph1), Ring1 (Ring1A) and Cbx2 (M33), and histone H3 acetylated on lysine 9 (H3K9) bind to flanking regions of the Hoxb8 gene. In 12.5 dpc embryos, association of Rnf2 to known Hoxb8 cis-acting regulatory elements was found predominantly in anterior embryonic tissues where transcription of this Hox gene is silent, whereas the presence of Edr1 and Cbx2 was observed irrespective of Hox transcriptional states. Conversely, acetylation of H3K9 at Hoxb8 was found in caudally increasing amounts in embryos, corresponding with the distribution of transcriptional activity. These results, and the developmental profile of Rnf2 association and H3K9 acetylation across the Hoxb cluster, suggest that inversely graded amounts of Rnf2-containing PcG complex and acetylated H3K9, may be involved in maintaining the anterior boundaries of Hox gene expression.

为了解决Polycomb组（PcG）介导的Hox基因表达抑制的分子机制，我们专注于PcG蛋白，Rnf 2（Ring 1B），Edr 1（Rae 28/Mph 1），Ring 1（Ring 1A）和Cbx 2（M33），以及组蛋白H3乙酰化赖氨酸9（H3 K9）结合到Hoxb 8基因的侧翼区域。在12.5 dpc的胚胎，协会的Rnf 2已知的Hoxb 8顺式作用调控元件被发现主要在前胚胎组织中，该Hox基因的转录是沉默的，而存在的Edr 1和Cbx 2观察到的Hox转录状态无关。相反，乙酰化H3 K9在Hoxb 8被发现在尾部增加量的胚胎，相应的转录活性的分布。这些结果，和发展概况的Rnf 2协会和H3 K9乙酰化的Hoxb集群，表明，反向梯度的Rnf 2的量含有PcG复合物和乙酰化H3 K9，可能参与维持Hox基因表达的前边界。

项目成果

Suzuki, M: "Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice"Development. 129. 4171-4183 (2002)

Suzuki, M：“多梳族基因 Ring1B 参与小鼠前后轴的规范”开发。

Yamaki, M: "The mouse Edr2 (Mph2) gene has two forms of mRNA encoding 90-and 36-kDa polyeptides"Gene. 288. 103-110 (2002)

Yamaki, M：“小鼠 Edr2 (Mph2) 基因有两种形式的编码 90-kDa 和 36-kDa 多肽的 mRNA”基因。

Yamada R., Mizutani-Koseki Y., Hasegawa T., Osumi N., Koseki H., Takahashi N.: "Cell-autonomous involvement of Mab21/1 is essential for lens placode development."Development. 130. 1759-1770 (2003)

Yamada R.、Mizutani-Koseki Y.、Hasekawa T.、Osumi N.、Koseki H.、Takahashi N.：“Mab21/1 的细胞自主参与对于晶状体基板的开发至关重要。”开发。

d Graaff W: "Randomly inserted and targeted Hox/reporter fusions transcriptionally silenced in Polycomb mutants."Proc Natl Acad Sci U S A. 22. 13362-13367 (2003)

d Graaff W：“随机插入和靶向的 Hox/报告基因融合在 Polycomb 突变体中转录沉默。”Proc Natl Acad Sci U S A. 22. 13362-13367 (2003)

Miyagishima, H.: "Dissociation of mammalian Polycomb-group proteins, Ring1B and Rae28/Ph1, from the chromatin correlates with configuration changes of the chromatin in mitotic and meiotic prophase."Histochem Cell Biol. 120. 111-119 (2003)

Miyagishima, H.：“哺乳动物多梳族蛋白 Ring1B 和 Rae28/Ph1 从染色质中解离，与有丝分裂和减数分裂前期染色质的构型变化相关。”《组织化学细胞生物学》。