Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors.
Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors.
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DOI：
10.1101/gad.301887.117
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发表时间：
2018-01-15
影响因子：
10.5
通讯作者：
Kohyama J
中科院分区：
文献类型：
--
作者：
Chai M;Sanosaka T;Okuno H;Zhou Z;Koya I;Banno S;Andoh-Noda T;Tabata Y;Shimamura R;Hayashi T;Ebisawa M;Sasagawa Y;Nikaido I;Okano H;Kohyama J
Chai等人表明，CHD7是超增强子和CNS特异性增强子的表观遗传激活所必需的，这支持神经上皮和CNS谱系身份的维持。多种先天性疾病通常表现为复杂的表型，但个体遗传因素的突变如何导致多种缺陷仍然知之甚少。在本研究中，我们使用人类神经上皮（NE）细胞和CHARGE患者来源的细胞作为体外模型系统，以确定染色体结构域解旋酶DNA结合7（CHD7）在NE神经嵴分叉的功能，从而揭示了中枢神经系统（CNS）和CHARGE综合征中观察到的颅面异常之间的病因联系。我们发现CHD7是表观遗传激活超增强子和CNS特异性增强子所必需的，这支持维持NE和CNS谱系身份。此外，我们发现BRN2和SOX 21是CHD7的下游效应子，CHD7通过增强CNS特异性细胞程序和间接抑制非CNS特异性细胞程序来塑造细胞身份。根据我们的研究结果，CHD7，通过其与超增强因子的相互作用，作为一个调节枢纽的编排的时空动态的转录因子，以调节NE和CNS谱系的身份。
Chai et al. show that CHD7 is required for epigenetic activation of superenhancers and CNS-specific enhancers, which support the maintenance of the neuroepithelial and CNS lineage identities. Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function of chromodomain helicase DNA-binding 7 (CHD7) in NE–neural crest bifurcation, thus revealing an etiological link between the central nervous system (CNS) and craniofacial anomalies observed in CHARGE syndrome. We found that CHD7 is required for epigenetic activation of superenhancers and CNS-specific enhancers, which support the maintenance of the NE and CNS lineage identities. Furthermore, we found that BRN2 and SOX21 are downstream effectors of CHD7, which shapes cellular identities by enhancing a CNS-specific cellular program and indirectly repressing non-CNS-specific cellular programs. Based on our results, CHD7, through its interactions with superenhancer elements, acts as a regulatory hub in the orchestration of the spatiotemporal dynamics of transcription factors to regulate NE and CNS lineage identities.
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影响因子：
3.7
作者：
Fukuta M;Nakai Y;Kirino K;Nakagawa M;Sekiguchi K;Nagata S;Matsumoto Y;Yamamoto T;Umeda K;Heike T;Okumura N;Koizumi N;Sato T;Nakahata T;Saito M;Otsuka T;Kinoshita S;Ueno M;Ikeya M;Toguchida J
通讯作者：
Toguchida J
影响因子：
9.2
作者：
Brown, JM;Storey, KG
通讯作者：
Storey, KG
影响因子：
3.7
作者：
Hagiwara K;Obayashi T;Sakayori N;Yamanishi E;Hayashi R;Osumi N;Nakazawa T;Nishida K
通讯作者：
Nishida K
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
DOI：
10.1126/science.aad7038
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Habib N;Li Y;Heidenreich M;Swiech L;Avraham-Davidi I;Trombetta JJ;Hession C;Zhang F;Regev A
通讯作者：
Regev A