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hox基因表达的抑制抑制hox基因表达的分子机制，我们重点介绍了PCG蛋白，RNF2（RING1B），EDR1（RAE28/MPH1）（RAE28/MPH1）（RING1（RING1）（RING1A）（RING1A）和CBX2（M33）和CBX2（M33）以及H3乙烯基上的lysiny 9（H3）（H3）（H3）（H3）（H3）基因。在12.5 DPC胚胎中，RNF2与已知的HOXB8顺式作用调节元件的关联主要在前胚胎组织中发现，在这些胚胎组织中，该HOX基因的转录是静默的，而EDR1和CBX2的存在是无关的。相反，在胚胎中发现了hoxb8上H3K9的乙酰化，胚胎量增加，与转录活性的分布相对应。这些结果，以及整个HOXB簇的RNF2关联和H3K9乙酰化的发育概况，表明含量分级的含有RNF2的PCG复合物和乙酰化H3K9可能与维持HOX基因表达的前边界有关。

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。

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》。

Fukuda, K: "Mesenchymal expression of Foxl1, a winged helix transcriptional factor, regulates generation and maintenance of gut associated lymphoid organs"Dev.Biol.. (In press). (2003)

Fukuda, K：“Foxl1（一种翼状螺旋转录因子）的间充质表达，调节肠道相关淋巴器官的生成和维持”Dev.Biol..（正在出版）。