Interplay Between Architectural Proteins In Stem Cell Chromatin Epigenetically Regulates Neural Developmet

Authors

• T Deng
• Y Postnikov
• S Zhang
• M Bustin

Abstract

Oligodendrocytes produce the myelin sheath covering neuron axons thus playing an essential role in central nervous system development, but the molecular mechanisms regulating oligodendrocyte differentiation are not fully known. We find that the nucleosome binding proteins HMGN1 and HMGN2 regulate the expression of OLIG1 and OLIG2, transcription factors crucial for oligodendrocyte development, and are required for proper oligodendrocyte development and axon myelination. Loss of HMGNs increases the chromatin binding of histone H1, thereby recruiting the histone methyltransferase EZH2 and elevating H3K27me3 levels, thus conferring a repressive epigenetic signature at Olig1&2 sites. Embryonic stem cells lacking HMGNs show reduced ability to differentiate towards the oligodendrocyte lineage, and mice lacking HMGNs show reduced oligodendrocyte count and decreased spinal cord myelination, and display related neurological phenotypes. Thus, the dynamic interplay between HMGNs and H1 in chromatin epigenetically regulates the expression of OLIG1&2, thereby affecting oligodendrocyte development and myelination, and mouse behavior.

Scientific Focus Area: Chromosome Biology

This page was last updated on Friday, March 26, 2021