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MyoD is a structure organizer of 3D genome architecture in muscle cells

By Qian Chen, Fengling Chen, Ruiting Wang, Minglei Shi, Antony K. Chen, Zhao Ma, Guohong Li, Min Wang, Hu Li, Xu Zhang, Jinbiao Ma, Jiayun Zhong, Meihong Chen, Michael Q. Zhang, Yong Zhang, Yang Chen, Dahai Zhu

Posted 30 Aug 2020
bioRxiv DOI: 10.1101/2020.08.29.273375

The genome is not a linear molecule of DNA randomly folded in the nucleus, but exists as an organized, three-dimensional (3D) dynamic architecture. Intriguingly, it is now clear that each cell type has a unique and characteristic 3D genome organization that functions in determining cell identity during development. A currently challenging basic question is how cell-type specific 3D genome structures are established during development. Herein, we analyzed 3D genome structures in primary myoblasts and myocytes from MyoD knockout (MKO) and wild type (WT) mice and discovered that MyoD, a pioneer transcription factor (TF), can function as a “genome organizer” that specifies the proper 3D genome architecture unique to muscle cell development. Importantly, we genetically demonstrate that H3K27ac is insufficient for establishing MyoD-induced chromatin loops in muscle cells. The establishment of MyoD’s “architectural role” should have profound impacts on advancing understanding of other pioneer transcription factors in orchestrating lineage specific 3D genome organization during development in a potentially very large number of cell types in diverse organisms. ### Competing Interest Statement The authors have declared no competing interest.

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