PU.1 as a chromatin accessibility factor for immunoglobulin genes

The hematopoietic-specific transcription factor PU.1 is a chromatin accessibility factor, based on analysis of the immunoglobulin heavy chain intronic (μ) enhancer. Whether PU.1 functions as an accessibility factor for additional PU.1-regulated genes is unknown. Outside the constraints of chromatin, PU.1 binds and activates transcription through both μ and κ3′ immunoglobulin enhancers, among others. The DNA-binding ETS domain of PU.1 is sufficient for activating both enhancers in an extrachromosomal context. New data show that the ETS domain of PU.1 is sufficient for increasing accessibility of a closed μ enhancer chromatin structure proximal to the PU.1-binding site. In contrast, PU.1 does not alter widespread chromatin accessibility. Furthermore, PU.1 does not induce accessibility proximal or distal to its binding site on the κ3′ enhancer. Taken together the data demonstrate that PU.1 induces chromatin accessibility proximal to its binding site at a locus activated early in development, the μ locus. PU.1 does not function as an accessibility factor for the κ3′ enhancer, which regulates a locus important for later stages of B cell development. We conclude that PU.1 is a context-dependent chromatin accessibility factor that, alone, cannot establish widespread accessibility required for critical developmental processes such as antigen receptor recombination.