BRG1 generates subnucleosomes that expand OCT4 binding and function beyond DNA motifs at enhancers

Abstract

AbstractBRG1, the catalytic subunit of the mammalian SWI/SNF complexes, is essential for chromatin opening at enhancers. However, the nature of the open chromatin remains unclear. Here we show that in addition to producing histone-free DNA, BRG1 generates hemisome-like subnucleosomal particles containing the four core histones associated with 50-80 base pairs of DNA. Our genome-wide analysis indicates that BRG1 makes these particles by targeting and splitting fragile nucleosomes. In mouse embryonic stem cells, these subnucleosomes become anin vivobinding substrate for the master transcription factor OCT4 independently of the presence of OCT4 DNA motifs. At enhancers, the OCT4-subnucleosome interaction increases OCT4 occupancy and amplifies the genomic interval bound by OCT4 by up to one order of magnitude, compared to the region occupied on histone-free DNA. We suggest that BRG1-dependent subnucleosomes orchestrate an epigenetic mechanism that projects OCT4 function in chromatin opening beyond its DNA motifs.