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DOI | 10.1038/s41586-018-0472-9 |
Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates | |
Mall, Moritz1,2; Kareta, Michael S.1,2,12; Chanda, Soham1,2,3,4; Ahlenius, Henrik5,6; Perotti, Nicholas1,2; Zhou, Bo1,2,3,4; Grieder, Sarah D.1,2; Ge, Xuecai7,13; Drake, Sienna5,6; Ang, Cheen Euong1,2; Walker, Brandon M.1,2; Vierbuchen, Thomas1,2,14; Fuentes, Daniel R.1,2; Brennecke, Philip8,15; Nitta, Kazuhiro R.9,16; Jolma, Arttu9; Steinmetz, Lars M.10; Taipale, Jussi9,11; Sudhof, Thomas C.3,4; Wernig, Marius1,2 | |
2017-04-13 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 544期号:7649页码:245-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Sweden; Germany; Finland; Japan |
英文摘要 | Normal differentiation and induced reprogramming require the activation of target cell programs and silencing of donor cell programs(1,2). In reprogramming, the same factors are often used to reprogram many different donor cell types3. As most developmental repressors, such as RE1-silencing transcription factor (REST) and Groucho (also known as TLE), are considered lineage-specific repressors(4,5), it remains unclear how identical combinations of transcription factors can silence so many different donor programs. Distinct lineage repressors would have to be induced in different donor cell types. Here, by studying the reprogramming of mouse fibroblasts to neurons, we found that the pan neuron-specific transcription factor Myt1-like (Myt1l)(6) exerts its pro-neuronal function by direct repression of many different somatic lineage programs except the neuronal program. The repressive function of Myt1l is mediated via recruitment of a complex containing Sin3b by binding to a previously uncharacterized N-terminal domain. In agreement with its repressive function, the genomic binding sites of Myt1l are similar in neurons and fibroblasts and are preferentially in an open chromatin configuration. The Notch signalling pathway is repressed by Myt1l through silencing of several members, including Hes1. Acute knockdown of Myt1l in the developing mouse brain mimicked a Notch gain-of-function phenotype, suggesting that Myt1l allows newborn neurons to escape Notch activation during normal development. Depletion of Myt1l in primary postmitotic neurons de-repressed non-neuronal programs and impaired neuronal gene expression and function, indicating that many somatic lineage programs are actively and persistently repressed by Myt1l to maintain neuronal identity. It is now tempting to speculate that similar 'many-but-one' lineage repressors exist for other cell fates; such repressors, in combination with lineage-specific activators, would be prime candidates for use in reprogramming additional cell types. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000398897900040 |
WOS关键词 | FINGER TRANSCRIPTION FACTORS ; LATERAL INHIBITION ; NERVOUS-SYSTEM ; EXPRESSION ; FAMILY ; GENES ; DIFFERENTIATION ; BINDING ; CELLS ; FIBROBLASTS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202961 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Stanford Univ, Dept Pathol, Stanford, CA 94305 USA; 2.Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Stanford, CA 94305 USA; 3.Stanford Univ, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA; 4.Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA; 5.Lund Univ, Div Neurol, Dept Clin Sci, S-22184 Lund, Sweden; 6.Lund Univ, Lund Stem Cell Ctr, S-22184 Lund, Sweden; 7.Stanford Univ, Dept Dev Biol, Stanford, CA 94305 USA; 8.Stanford Univ, Dept Genet, Stanford, CA 94305 USA; 9.Karolinska Inst, Dept Med Biochem & Biophys, Div Funct Genom & Syst Biol, S-17177 Stockholm, Sweden; 10.EMBL, Genome Biol Unit, D-69117 Heidelberg, Germany; 11.Univ Helsinki, Genome Scale Biol, Helsinki 00014, Finland; 12.Genet & Genom Grp, Sanford Res, Sioux Falls, SD 57104 USA; 13.Univ Calif Merced, Mol & Cellular Biol, Merced, CA 95343 USA; 14.Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA; 15.Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany; 16.RIKEN Ctr Life Sci Technol, Div Genom Technol, Yokohama, Kanagawa 2300045, Japan |
推荐引用方式 GB/T 7714 | Mall, Moritz,Kareta, Michael S.,Chanda, Soham,et al. Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates[J]. NATURE,2017,544(7649):245-+. |
APA | Mall, Moritz.,Kareta, Michael S..,Chanda, Soham.,Ahlenius, Henrik.,Perotti, Nicholas.,...&Wernig, Marius.(2017).Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates.NATURE,544(7649),245-+. |
MLA | Mall, Moritz,et al."Myt1l safeguards neuronal identity by actively repressing many non-neuronal fates".NATURE 544.7649(2017):245-+. |
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