Histone modification is a well-studied mechanism to transiently adjust chromatin density.  Pioneer factors can play a role in this by binding specific enhancers and flagging histone modification enzymes to that specific gene.  Repressive pioneer factors can inhibit transcription by recruiting factors that modify histones that further tighten the chromatin.  This is important to limit gene expression to specific cell types and has to be removed only when cell differentiation begins.  FoxD3 has been associated as a repressor of both B-cell and melanocytic cell differentiation pathways, maintaining repressive histone modifications where bound, that have to be overcome to start differentiation.  Pioneer factors can also be associated with recruiting transcription-activating histone modifications.  Enzymes that modify H3K4 with mono and di-methylation are associated with increasing transcription and have been shown to bind pioneer factors.  In B cell differentiation PU.1 is necessary to signal specific histones for activating H3K4me1 modifications that differentiate hematopoietic stem cells into either the B-cell or macrophage lineage.  FoxA1 binding induces HSK4me2 during neuronal differentiation of pluripotent stem cells  as well as the loss of DNA methylation. SOX9 recruits histone modification enzymes MLL3 and MLL4 to deposit H3K4me1 prior to the opening of enhancers in developing hair follicle and basal cell carcinoma.