Chromatin remodeler CHD7 targets active enhancer region to regulate cell type-specific gene expression in human neural crest cells.
Chromatin remodeler CHD7 targets active enhancer region to regulate cell type-specific gene expression in human neural crest cells.
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染色质重塑剂 CHD7 靶向活性增强子区域，调节人神经嵴细胞中细胞类型特异性基因表达。
DOI：
10.1038/s41598-022-27293-6
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发表时间：
2022-12-31
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
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染色质重塑染色体结构域解旋酶DNA结合7（CHD 7）基因突变导致多发性先天性异常CHARGE综合征。在CHARGE综合征中观察到的颅面异常是由起源于神经管的神经嵴细胞（NCC）功能障碍引起的。然而，CHD 7调节人类NCC（hNCC）功能的机制仍不清楚。我们的目的是通过分析全基因组ChIP-Seq数据和鉴定hNCC特异性CHD 7结合谱来表征hNCC中由CHD 7控制的顺式调控元件。我们比较了CHD 7结合区域之间的细胞类型，包括人类诱导多能干细胞和人类神经上皮细胞，以确定CHD 7结合在hNCC的综合性能。重要的是，对hNCC特异性CHD 7结合区域的分析揭示了转录因子AP-2α作为促进hNCC中细胞类型特异性转录程序的潜在辅因子。CHD 7与活性增强子区域密切相关，允许hNCC特异性基因的表达以维持hNCC的功能。我们的研究结果揭示了CHD 7在hNCC中的调控机制，从而提供了关于hNCC中转录程序的额外信息。
A mutation in the chromatin remodeler chromodomain helicase DNA-binding 7 (CHD7) gene causes the multiple congenital anomaly CHARGE syndrome. The craniofacial anomalies observed in CHARGE syndrome are caused by dysfunctions of neural crest cells (NCCs), which originate from the neural tube. However, the mechanism by which CHD7 regulates the function of human NCCs (hNCCs) remains unclear. We aimed to characterize the cis-regulatory elements governed by CHD7 in hNCCs by analyzing genome-wide ChIP-Seq data and identifying hNCC-specific CHD7-binding profiles. We compared CHD7-binding regions among cell types, including human induced pluripotent stem cells and human neuroepithelial cells, to determine the comprehensive properties of CHD7-binding in hNCCs. Importantly, analysis of the hNCC-specific CHD7-bound region revealed transcription factor AP-2α as a potential co-factor facilitating the cell type-specific transcriptional program in hNCCs. CHD7 was strongly associated with active enhancer regions, permitting the expression of hNCC-specific genes to sustain the function of hNCCs. Our findings reveal the regulatory mechanisms of CHD7 in hNCCs, thus providing additional information regarding the transcriptional programs in hNCCs.
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DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
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作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
影响因子：
10.5
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
通讯作者：
Kohyama J
DOI：
10.1073/pnas.1010740107
发表时间：
2011-01-04
影响因子：
11.1
作者：
de Croze, Noemie;Maczkowiak, Frederique;Monsoro-Burq, Anne H.
通讯作者：
Monsoro-Burq, Anne H.
影响因子：
3.5
作者：
Ciptasari U;van Bokhoven H
通讯作者：
van Bokhoven H
影响因子：
64.8
作者：
通讯作者：
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