MyoD is a 3D genome structure organizer for muscle cell identity

Ruiting Wang,Yong Zhang,Yachen Ying,Michael Q Zhang,Meihong Chen,Jinbiao Ma,Yang Chen,Zhao Ma,Min Wang,Qian Chen,Fengling Chen,Xu Zhang,Guohong Li,Antony K Chen,Minglei Shi,Qinyao Liu,Jun Zhong ,Xin Wan ,Hu Li,Dahai Zhu

doi:10.1038/s41467-021-27865-6

Abstract

The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a “genome organizer” that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.

Highlights

The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity
Considering our finding that MyoD apparently functions together with CTCF to regulate the insulation of contact domain boundaries (CDBs), we questioned whether MyoD might control the formation of chromatin loops in 50 kb a aggregate peak analysis (APA):2.73 max:25.53
The cell-type-specific organization of the 3D genome can be regarded as an emergent property that is mediated by the interplay between transcription factor (TF) and chromatin-associated proteins[57]

Summary

Introduction

The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. MyoD (myogenic differentiation 1) and Myf[5] are members of the myogenic regulatory factor (MRF) family and are expressed in somites[12,13,14,15] These proteins function as a basic helix–loop–helix transcription factors and are required for myogenic determination during early embryogenesis. The single inactivation of either MyoD or Myf[5] in mice results in apparently normal muscle development but delayed myogenic differentiation[19,20,21,22] and impaired muscle regeneration[20] Together, these observations indicate that MyoD and Myf[5] can functionally compensate for one another during myogenic development[17,23]

Methods

Results

Conclusion