Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture.
Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture.
复制标题
内核蛋白Matrin-3通过稳定染色质结构协调细胞分化。
DOI：
10.1038/s41467-021-26574-4
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发表时间：
2021-10-29
影响因子：
16.6
通讯作者：
Orkin SH
中科院分区：
文献类型：
--
作者：
Cha HJ;Uyan Ö;Kai Y;Liu T;Zhu Q;Tothova Z;Botten GA;Xu J;Yuan GC;Dekker J;Orkin SH
在分化过程中基因表达的精确控制依赖于染色质和核结构的相互作用。尽管核膜蛋白对发育基因调控的贡献已经确定，但关于内核蛋白的作用知之甚少。在这里，我们证明了核支架蛋白Matrin-3（Matr 3）在红系细胞中的损失导致形态和基因表达的变化特征的加速成熟，以及广泛的染色质组织的变化类似于那些伴随分化。Matr 3蛋白与CTCF和粘附素复合物相互作用，其丢失扰乱了它们在一个位点子集的占据。CTCF和粘附素结合的不稳定性与转录改变和加速分化相关。这种关联在胚胎干细胞中是保守的。我们的研究结果表明，Matr 3对细胞命运的转变产生负面影响，并表明一个关键的内核蛋白影响建筑因子的占用，最终对染色质组织和细胞分化产生广泛的影响。染色质和核成分之间的相互作用以及这些相互作用是否影响发育还不清楚。在这里，作者表明内核蛋白Matrin-3（Matr 3）的丢失导致加速红细胞成熟，并且Matr 3参与染色体结构组织和区室化以负调节细胞分化。
Precise control of gene expression during differentiation relies on the interplay of chromatin and nuclear structure. Despite an established contribution of nuclear membrane proteins to developmental gene regulation, little is known regarding the role of inner nuclear proteins. Here we demonstrate that loss of the nuclear scaffolding protein Matrin-3 (Matr3) in erythroid cells leads to morphological and gene expression changes characteristic of accelerated maturation, as well as broad alterations in chromatin organization similar to those accompanying differentiation. Matr3 protein interacts with CTCF and the cohesin complex, and its loss perturbs their occupancy at a subset of sites. Destabilization of CTCF and cohesin binding correlates with altered transcription and accelerated differentiation. This association is conserved in embryonic stem cells. Our findings indicate Matr3 negatively affects cell fate transitions and demonstrate that a critical inner nuclear protein impacts occupancy of architectural factors, culminating in broad effects on chromatin organization and cell differentiation. Interactions between chromatin and nuclear components and whether these interactions affect development is not well understood. Here the authors show inner nuclear protein Matrin-3 (Matr3) loss leads to accelerated erythroid maturation, and that Matr3 is involved in chromosomal structure organization and compartmentalization to negatively regulate cell differentiation.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
7
作者：
Beagan JA;Duong MT;Titus KR;Zhou L;Cao Z;Ma J;Lachanski CV;Gillis DR;Phillips-Cremins JE
通讯作者：
Phillips-Cremins JE
影响因子：
9.3
作者：
Durand NC;Shamim MS;Machol I;Rao SS;Huntley MH;Lander ES;Aiden EL
通讯作者：
Aiden EL
DOI：
10.3791/52118
发表时间：
2015-01-03
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Bauer DE;Canver MC;Orkin SH
通讯作者：
Orkin SH