Recruitment of a chromatin remodeler primes macrophage-specific genes
Recruitment of the nucleosome remodeler SWI/SNF to enhancers of macrophage-specific genes prevents high levels of nucleosome occupancy at these sites in macrophages (McAndrew et al. 2016). We used an shRNA approach to knockdown specific SWI/SNF subunits in hematopoietic progenitors that were then differentiated into BMDMs. Our data show that recruitment of SWI/SNF is mediated directly or indirectly by the macrophage-specific pioneer transcription factor PU.1, which binds to macrophage-specific genes early on during differentiation. This facilitates binding of signal-induced transcription factors and gene expression in mature macrophages in response to an appropriate signal.
We propose that the remodeler functions by increasing nucleosome turn-over to promote transcription factor binding in a process we have termed remodeler assisted competition of transcription factors with nucleosomes. Our results indicate that the SWI/SNF remodeler functions at cell-type specific genes long before the genes are actually expressed. Thus, as a cell differentiates into a specific cell-type it acquires all the necessary information early on that then dictates its behavior as an adult cell. It remains to be investigated how changes in the environment during differentiation can influence the behavior of a mature cell, or in other words how epigenetic effects during differentiation affect gene expression in an adult cell.