SMYD2 Drives Mesendodermal Differentiation of Human Embryonic Stem Cells Through Mediating the Transcriptional Activation of Key Mesendodermal Genes
文献类型：期刊论文
| 作者 | Bai, Hua-Jun2; Zhang, Peng2; Liang, He2; Yang, Huang-Tian2; Ma, Li1; Wei, Gang1; , |
| 刊名 | STEM CELLS
 |
| 出版日期 | 2019 |
| 卷号 | 37期号:11页码:1401-1415 |
| ISSN号 | 1066-5099 |
| 关键词 | Human embryonic stem cells SET and MYND domain-containing protein 2 Histone methyltransferase Mesendodermal differentiation Brachyury Eomesodermin Mix paired-like homeobox Goosecoid homeobox |
| DOI | 10.1002/stem.3068 |
| 文献子类 | Article |
| 英文摘要 | Histone methyltransferases play a critical role in early human development, whereas their roles and precise mechanisms are less understood. SET and MYND domain-containing protein 2 (SMYD2) is a histone lysine methyltransferase induced during early differentiation of human embryonic stem cells (hESCs), but little is known about its function in undifferentiated hESCs and in their early lineage fate decision as well as underlying mechanisms. Here, we explored the role of SMYD2 in the self-renewal and mesendodermal lineage commitment of hESCs. We demonstrated that the expression of SMYD2 was significantly enhanced during mesendodermal but not neuroectodermal differentiation of hESCs. SMYD2 knockout (SMYD2(-/-)) did not affect self-renewal and early neuroectodermal differentiation of hESCs, whereas it blocked the mesendodermal lineage commitment. This phenotype was rescued by reintroduction of SMYD2 into the SMYD2(-/-) hESCs. Mechanistically, the bindings of SMYD2 at the promoter regions of critical mesendodermal transcription factor genes, namely, brachyury (T), eomesodermin (EOMES), mix paired-like homeobox (MIXL1), and goosecoid homeobox (GSC) were significantly enhanced during mesendodermal differentiation of SMYD2(+/+) hESCs but totally suppressed in SMYD2(-/-) ones. Concomitantly, such a suppression was associated with the remarkable reduction of methylation at histone 3 lysine 4 and lysine 36 but not at histone 4 lysine 20 globally and specifically on the promoter regions of mesendodermal genes, namely, T, EOMES, MIXL1, and GSC. These results reveal that the histone methyltransferase SMYD2 is dispensable in the undifferentiated hESCs and the early neuroectodermal differentiation, but it promotes the mesendodermal differentiation of hESCs through the epigenetic control of critical genes to mesendodermal lineage commitment. Stem Cells 2019;37:1401-1415 |
| 学科主题 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| WOS关键词 | CARDIAC DIFFERENTIATION ; LYSINE METHYLATION ; FATE DECISIONS ; GERM LAYER ; EXPRESSION ; IDENTIFICATION ; PROLIFERATION ; DEMETHYLASE ; ANNOTATION ; ENCODES |
| 语种 | 英语 |
| CSCD记录号 | CSCD:31348575 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000493274100005 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1203]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci, Univ Chinese Acad Sci CAS, SIBS,CAS MPG Partner Inst Computat Biol, CAS Key Lab Computat Biol,Lab Epigenome Biol,Shan, Shanghai, Peoples R China, 2.Chinese Acad Sci, Univ Chinese Acad Sci CAS, SIBS,Shanghai Inst Nutr & Hlth, CAS Key Lab Tissue Microenvironm & Tumor,Lab Mol, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Bai, Hua-Jun,Zhang, Peng,Liang, He,et al. SMYD2 Drives Mesendodermal Differentiation of Human Embryonic Stem Cells Through Mediating the Transcriptional Activation of Key Mesendodermal Genes[J]. STEM CELLS,2019,37(11):1401-1415. |
| APA | Bai, Hua-Jun.,Zhang, Peng.,Liang, He.,Yang, Huang-Tian.,Ma, Li.,...&,.(2019).SMYD2 Drives Mesendodermal Differentiation of Human Embryonic Stem Cells Through Mediating the Transcriptional Activation of Key Mesendodermal Genes.STEM CELLS,37(11),1401-1415. |
| MLA | Bai, Hua-Jun,et al."SMYD2 Drives Mesendodermal Differentiation of Human Embryonic Stem Cells Through Mediating the Transcriptional Activation of Key Mesendodermal Genes".STEM CELLS 37.11(2019):1401-1415. |
入库方式： OAI收割
来源：上海营养与健康研究所
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