Elucidation of the diversity of target genes in GATA1

阐明GATA1中靶基因的多样性

• 批准号: 24890015
• 负责人: KANEKO Hiroshi
• 金额: $ 2.33万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-08-31 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24890015/
• 关键词: 遺伝子発現制御; GATA因子; 転写活性化部位; 転写因子; GATA転写因子; 細胞分化; マイクロアレイ解析; トランスジェニックマウス; ノックアウトマウス

Transcription factor GATA1 has two distinct transactivation domains (N-TAD and C-TAD). It remains to be uncovered what these multiple TADs systems confers on GATA1 function in vivo. In this study, I revealed that GATA1 target genes were classified into three groups with their dependency to TAD. In addition to this GST-pull down assay showed that GATA1 and Rb interaction was dependent to N-TAD. Because, GATA1 mutations which causes the deletion of N-TAD are found in Down's related acute megakaryoblastic leukemia(DS-AMkL) and transient myeoproliferative disorder(TMD), this result suggests that GATA1 transcriptional regulatory mechanism based on multiple TAD system is involvement to the pathology of DS-AMkL and TMD.

转录因子GATA 1具有两个不同的转录激活结构域（N-fos和C-fos）。这些多个TADs系统在体内赋予GATA 1功能的作用仍有待揭示。在这项研究中，我揭示了GATA 1靶基因被分为三组，其依赖于ESTA。除此之外，GST-下拉测定显示GATA 1和Rb相互作用依赖于N-组氨酸。由于在Down’s related acute megakaryoblasting leukemia（DS-AMkL）和一过性myeoproliferative disorder（TMD）中发现了导致N-fos缺失的GATA 1突变，因此，这一结果提示基于多转录系统的GATA 1转录调控机制参与了DS-AMkL和TMD的病理过程。

项目成果

N- and C- terminal transactivation domain of GATA1 protein coordinate hematopoietic program

GATA1蛋白的N端和C端反式激活结构域协调造血程序

• 发表时间: 2012
• 期刊: J. Biol. Chem
• 作者: Kaneko H;Kobayashi E;Yamamoto M;Shimizu R
• 通讯作者: Shimizu R

N- and C-terminal Transactivation Domains of GATA1 Protein Coordinate Hematopoietic Program

• DOI: 10.1074/jbc.m112.370437
• 发表时间: 2012-06-15
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Kaneko, Hiroshi;Kobayashi, Eri;Shimizu, Ritsuko
• 通讯作者: Shimizu, Ritsuko

Naturally occurring oncogenic GATA1 mutations with internal deletions in transient abnormal myelopoiesis in Down Syndrome

唐氏综合症短暂异常骨髓生成​​中自然发生的致癌 GATA1 突变及内部缺失

• 发表时间: 2013
• 期刊: Blood
• 影响因子: 20.3
• 作者: Toki T;Kanezaki R;Kobayashi E;Kaneko H;et al
• 通讯作者: et al