Analysis of regulatory mechanisms of epigenetic gene regulation by a complex of nuclear matrix protein and noncoding RNA

核基质蛋白与非编码RNA复合物对表观遗传基因调控的调控机制分析

• 批准号: 23370093
• 负责人: NAKAGAWA Shinichi
• 金额: $ 12.65万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23370093/
• 关键词: 核マトリクス; hnRNP U; インプリンティング; アリル特異的発現; ノンコーディングRNA; Xist; X染色体; ゲノムインプリンティング; Airn; Kcnqlot1; クロマチン免疫沈降; クロスリンク免疫沈降

In the human and mouse, vast majority of the genome is transcribed into RNAs, producing a huge number of non protein-coding RNAs. These noncoding RNAs associate with chromatin-modifying complexes, and are assumed to regulate epigenetic gene expression. In this study, we have performed functional analysis of a nuclear matrix protein hnRNP U that regulate chromosomal localization of Xist, a renowned noncoding RNA involved in the X chromosome inactivation. We found that hnRNP U also regulates the chromosomal localization and function of noncoding RNAs such as Kcnq1ot1 and Airn, and the allele-specific expression of the imprinted loci were impaired upon depletion of hnRNP U. We also performed genome-wide gene expression analysis of the hnRNP U depleted cells, and found that multiple allele-specific expression were also disturbed. We found a novel noncoding RNA expressed from the allele-specific locus, and its transcripts were also associated with the chromosome in a mono-allelic manner.

在人类和小鼠中，绝大多数基因组被转录成RNA，产生大量非蛋白质编码的RNA。这些非编码RNA与染色质修饰复合体相关，并被认为调节表观遗传基因的表达。在本研究中，我们对核基质蛋白hnRNP U进行了功能分析，该蛋白调节Xist的染色体定位，Xist是一种著名的非编码RNA，参与X染色体失活。我们发现hnRNP U还调节Kcnq1ot1和AIRN等非编码RNA的染色体定位和功能，当hnRNP U耗尽时，印迹基因座的等位基因特异性表达受到损害。我们还对hnRNP U耗尽的细胞进行了全基因组基因表达分析，发现多个等位基因特异性表达也受到干扰。我们发现了一种新的非编码RNA，它的转录本也以单等位基因的方式与染色体相关。

项目成果

Gathering around Firre

聚集在Firre周围

• DOI: 10.1038/nsmb.2782
• 发表时间: 2014
• 期刊: Nat. Struc.t Mol. Biol
• 作者: Nakagawa;S. and Hirano;T
• 通讯作者: T

中川真一「転移因子・ウイルスと宿主のせめぎ合いによりもたらされるゲノム進化」実験医学増刊号, 31 (7), 83-90 (2013)

中川真一，“转座因子/病毒与宿主之间的冲突带来的基因组进化”，实验医学特刊，31（7），83-90（2013）

Malat1 is not an essential component of nuclear speckles in mice

• DOI: 10.1261/rna.033217.112
• 发表时间: 2012-08-01
• 期刊: RNA
• 影响因子: 4.5
• 作者: Nakagawa, Shinichi;Ip, Joanna Y.;Prasanth, Kannanganattu V.
• 通讯作者: Prasanth, Kannanganattu V.

Nonessentials for nothing?-Nuclear bodies paraspeckles are not essential for animal's life

非必需品无用？-核体副斑点对动物的生命不是必需的

• 发表时间: 2011
• 作者: Kim Y.K.;Watanabe S.;Kaneko T.;et al.;T.Kanazawa;Shinichi Nakagawa
• 通讯作者: Shinichi Nakagawa

Functional analysis of nuclear long noncoding RNAs

核长非编码RNA的功能分析

• 发表时间: 2013
• 作者: 長谷川優子;中川真一;竹居孝二;山田 浩司;Shinichi Nakagawa
• 通讯作者: Shinichi Nakagawa