Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture

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. 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.

Automated summary

This study demonstrates that the loss of inner nuclear protein Matrin-3 (Matr3) accelerates erythroid maturation and negatively regulates cell differentiation by influencing chromosomal structure organization and compartmentalization. Matr3 interacts with CTCF and the cohesin complex, and its loss perturbs their occupancy at certain sites, leading to altered transcription and accelerated differentiation. These findings suggest a critical role of Matr3 in cell fate transitions through its impact on architectural factors and chromatin organization.