The important role of transcription factor MESP1 combined with epigenetic modification protein RING1A in heart development was published

Congenital heart disease is the most common birth defect in newborns, with an incidence of 0.
4%~1%.

Multiple mutations in the important transcription factor MESP1 during cardiac development are known as well as the epigenetic modification complexes PRC1 (Polycomb repressive complex 1) and the adhesin complex ( Cohesin) mutations in multiple components are strongly associated with the development of congenital heart disease[1-3]The specific mechanism of action of these components in cardiac development is unclear
.

On November 21, 2022, Sun Ning's team from the School of Basic Medicine of Fudan University and the School of Medicine of Wuxi of Jiangnan University and Lan Fei's team from the Institute of Biomedical Sciences (IBS) of Fudan University published an online report titled Essential role of MESP1-RING1A complex in Developmental Cell The work of
cardiac differentiation.

In order to further explore the molecular mechanism of action of MESP1, it was found that MESP1 can bind to the PRC1 core protein RING1A and found RING1A It plays an important role
in the in vitro differentiation of human cardiomyocytes and the development of mouse hearts.
The P RC1 complex mainly plays the role of inhibiting gene expression, and it has also been reported that P RC1 can participate in the activation of gene expression during some developmental processes, for example, P RC1 binds to AUTS2 to activate gene expression and participates in neural differentiation[4]
。 In this paper, it was further found that MESP1-RING1A can bind to the cohesin complex and activate the expression
of cardiac development genes by regulating chromatin interactions.

At the same time, it was found that the pathogenic mutation of MESP1 affects the binding of MESP1 to RING1A and cohesin components.
Affects the expression of cardiac development genes and the normal differentiation of myocardium
.
These studies not only demonstrate the importance of MESP1-RING1A in cardiac development, but also provide a possible explanation
for the mechanism by which mutations in the MESP1, PRC1 and cohesin components lead to congenital heart disease.

The transcription factor MESP1 and the epigenetic factor RING1A synergistically regulate early cardiac development

Professor Sun Ning and Prof.
Lan Fei are co-corresponding authors
of the paper.
Dr.
Siqing Wang, a young associate researcher at the School of Basic Medical Sciences, Fudan University, and a doctoral student at the School of Basic Medical Sciences, Zhou Xinyan, are co-first authors
.
The research has been supported
by the National Key R&D Program, Shanghai Science and Technology Major Project, National Natural Face Project, National Natural Youth Project, China Association for Science and Technology Young Talents Entrusted Project, China Postdoctoral Special Funding Project, etc.

Original link: https://doi.
org/10.
1016/j.
devcel.
2022.
10.
009

References:

[1]Werner P, Latney B, Deardorff M A, et al.
MESP1 Mutations in Patients with Congenital Heart Defects[J].
Human Mutation, 2016, 37(3): 308-314.

[2]Turnpenny P D, Wright M J, Sloman M, et al.
Missense mutations of the Pro65 residue of PCGF2 cause a recognizable syndrome associated with craniofacial, neurological, cardiovascular, and skeletal features[J].
The American Journal of Human Genetics, 2018, 103(5): 786-793.

[3]Piché J, Van Vliet P P, Pucéat M, et al.
The expanding phenotypes of cohesinopathies: one ring to rule them all![ J].
Cell Cycle, 2019, 18(21): 2828-2848.

[4]Liu S, Aldinger K A, Cheng C V, et al.
NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain[J].
Mol Cell, 2021, 81(22): 4757.