An Interplay Between Architectural Proteins In Stem Cell Chromatin Epigenetically Regulates OLIG1&2 Expression And Oligodendrocyte Differentiation. Mus musculus

The transcription factors OLIG1 and OLIG2 are crucial for oligodendrocyte lineage specification and nerve myelination, but the regulators of Olig1&2 expression are not known. We find that Olig1&2 expression is significantly down regulated in embryonic stem cells lacking HMGN1 and HMGN2, two ubiquitous nucleosome binding proteins that affect chromatin structure and function. Loss of HMGNs increases the nucleosome binding of histone H1 thereby recruiting the histone methyltransferase EZH2 and elevating H3K27me3 levels, thus conferring an epigenetic signature of repressed genes at Olig1&2 sites. ESCs lacking HMGNs show reduced ability to differentiate towards the oligodendrocyte lineage, and mice lacking HMGNs show reduced oligodendrocyte count and decreased myelination in their spinal cords and display neurological phenotypes. Thus, the dynamic interplay between HMGNs and H1 in the chromatin of ESCs epigenetically regulates the expression of OLIG1&2, thereby affecting oligodendrocyte lineage development and mouse behaviors.