H3K4 Methyltransferase Set1a Is A Key Oct4 Coactivator Essential for Generation of Oct4 Positive Inner Cell Mass
2016-03
发表期刊STEM CELLS
ISSN1066-5099
卷号34期号:3页码:565-580
发表状态已发表
DOI10.1002/stem.2250
摘要Limited core transcription factors and transcriptional cofactors have been shown to govern embryonic stem cell (ESC) transcriptional circuitry and pluripotency, but the molecular interactions between the core transcription factors and cofactors remains ill defined. Here, we analyzed the protein-protein interactions between Oct4, Sox2, Klf4, and Myc (abbreviated as OSKM) and a large panel of cofactors. The data reveal both specific and common interactions between OSKM and cofactors. We found that among the SET1/MLL family H3K4 methyltransferases, Set1a specifically interacts with Oct4 and this interaction is independent of Wdr5. Set1a is recruited to and required for H3K4 methylation at the Oct4 target gene promoters and transcriptional activation of Oct4 target genes in ESCs, and consistently Set1a is required for ESC maintenance and induced pluripotent stem cell generation. Gene expression profiling and chromatin immunoprecipitation-seq analyses demonstrate the broad involvement of Set1a in Oct4 transcription circuitry and strong enrichment at TSS sites. Gene knockout study demonstrates that Set1a is not only required for mouse early embryonic development but also for the generation of Oct4-positive inner cell mass. Together our study provides valuable information on the molecular interactions between OSKM and cofactors and molecular mechanisms for the functional importance of Set1a in ESCs and early development.
关键词Embryonic stem cells Epigenetics Induced pluripotent stem cells Transcription factors Targeted gene disruption
收录类别SCI
语种英语
资助项目Science and Technology Commission of Shanghai Municipality[14XD1401700] ; Science and Technology Commission of Shanghai Municipality[11DZ2260300]
WOS研究方向Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
WOS类目Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology
WOS记录号WOS:000372552600005
出版者WILEY
WOS关键词EMBRYONIC STEM-CELLS ; SELF-RENEWAL ; RNAI SCREEN ; TRANSCRIPTIONAL NETWORK ; HISTONE MODIFICATIONS ; SOMATIC-CELLS ; MOUSE EMBRYOS ; PLURIPOTENCY ; CHROMATIN ; MAINTENANCE
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1905
专题信息科学与技术学院_硕士生
生命科学与技术学院_PI研究组_黄行许组
通讯作者Wong, Jiemin
作者单位
1.E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200062, Peoples R China
2.E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China
3.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing 210008, Jiangsu, Peoples R China
4.Natl Resource Ctr Mutant Mice, Nanjing, Jiangsu, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
6.Tongji Univ, Sch Life Sci & Technol, Shanghai Key Lab Signaling & Dis Res, Shanghai 200092, Peoples R China
7.Indiana Univ Purdue Univ, Sch Sci, Dept Biol, Indianapolis, IN 46202 USA
8.Shanghai Jiao Tong Univ, Sch Med, Dept Mol Dev, Shanghai 200030, Peoples R China
9.Sun Yat Sen Univ, Ctr Canc, Collaborat Innovat Ctr Canc Med, Guangzhou 510275, Guangdong, Peoples R China
推荐引用方式
GB/T 7714
Fang, Lan,Zhang, Jun,Zhang, Hui,et al. H3K4 Methyltransferase Set1a Is A Key Oct4 Coactivator Essential for Generation of Oct4 Positive Inner Cell Mass[J]. STEM CELLS,2016,34(3):565-580.
APA Fang, Lan.,Zhang, Jun.,Zhang, Hui.,Yang, Xiaoqin.,Jin, Xueling.,...&Wong, Jiemin.(2016).H3K4 Methyltransferase Set1a Is A Key Oct4 Coactivator Essential for Generation of Oct4 Positive Inner Cell Mass.STEM CELLS,34(3),565-580.
MLA Fang, Lan,et al."H3K4 Methyltransferase Set1a Is A Key Oct4 Coactivator Essential for Generation of Oct4 Positive Inner Cell Mass".STEM CELLS 34.3(2016):565-580.
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