Site-specific phosphorylation of histone H1.4 is associated with transcription activation.

Core histone variants like H2A.X and H3.3 and their modified forms serve specialized roles in chromatin processes that depend on their genomic distributions and their interaction with chromatin components. Similarly, growing evidence from our lab and others suggest that amino acid sequence variant forms of the linker histone family and specific posttranslational modifications on these variants also result in distinct functions. These inferences are contrary to the notion that the H1 family function as redundant repressors. Here, we provide the first genome-wide evidence that when phosphorylated at a specific C-terminal domain site i.e serine 187, the linker histone H1.4 is enriched at active promoters. This is in direct contrast to previous reports that suggest that phosphorylation of H1 leads to their dissociation from chromatin. Using a novel and highly specific pS187H1.4 antibody developed in the lab, we studied the distribution patterns of pS187H1.4 in estradiol-responsive MCF7 cells where we demonstrated the inducible nature of this modification. We also used public MCF7 data to confirm the association of pS187H1.4 with well-known active transcription marks. These data suggest that linker histones and their modified forms have a more nuanced role than previously understood and may even play a role in transcription regulation.