Linker histone H1.5 contributes to centromere integrity

Mammalian H1 linker histones comprise a group of 11 non-allelic variants, which have key roles in modulating chromatin. H1-variant-specific genomic distribution may contribute to fine-tuning regulation of gene expression and chromatin architecture. Contradicting reports on the presence of H1 histones at centromeres led us to directly investigate whether H1 impacts centromeric chromatin. We report that three linker histone variants appear to physically interact with centromeric-protein A (CENP-A) mononucleosomes in vitro, including the variant H1.5. Probing this putative interaction in vivo, we observe that H1.5 localizes to the centromere in human cells, and chromatin immunoprecipitation supports a physical interaction between H1.5 and centromeric chromatin. Targeted depletion of H1.5 results in the loss of centromeric α-satellite transcription, reduction in loading of new CENP-A, alterations in kinetochore protein gene expression, and the accumulation of mitotic defects. Cumulatively, these data suggest an unreported role for specific histone H1 variants in the regulation of mitotic integrity.