BAHCC1 promotes gene expression in neuronal cells by antagonizing SIN3A-HDAC1

Chromatin modifications play a key role in the regulation of gene expression during development and adult physiology. Histone acetylation, and in particular H3K27ac is associated with increased activity of gene regulatory elements. The regulation of the machinery that deposits or strips this modification remains poorly understood. In particular, the SIN3A-HDAC1 complex possesses a histone deacetylation activity, yet it commonly resides at active regulatory regions. Here, we study BAHCC1, a large chromatin-associated protein essential for viability, and recently reported to play a largely repressive role. We show that in cells of the neuronal lineage, BAHCC1 is most associated with regulatory elements marked with H3K27ac. BAHCC1 interacts and co-occupies shared genomic regions with the SIN3A scaffold protein and its perturbations lead to decreased acetylation and decreased expression of the proximal genes in a neuronal cell line and in primary cortical neurons. The regulated genes are enriched for those functioning in neurogenesis and cell migration. We propose a model in which BAHCC1 antagonizes SIN3A histone deacetylation and positively regulates the expression of genes important in the neuronal lineage.