Gene-specific H1 eviction through a transcriptional activator-p300-NAP1-H1 pathway

By M. Shimada, Wei-Yi Chen, T. Nakadai, Takashi Onikubo, M. Guermah, D. Rhodes, R. Roeder. 2019

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SUMMARY Linker histone H1 has been correlated with transcriptional inhibition, but the mechanistic basis of the inhibition and its reversal during gene activation has remained enigmatic. We report that H1-compacted chromatin, reconstituted in vitro, blocks transcription by abrogating core histone modifications by p300 but not activator and p300 binding. Transcription from H1-bound chromatin is elicited by H1 chaperone NAP1, which is recruited in a gene-specific manner through direct interactions with activator-bound p300 that facilitate core histone acetylation (by p300) and concomitant eviction of H1 and H2A/H2B. An analysis in B cells confirms the strong dependency on NAP1-mediated H1 eviction for induction of the silent CD40 gene and further demonstrates that H1 eviction, seeded by activator-p300-NAP1 interactions, is propagated over a CTCF-demarcated region through a distinct mechanism that also involves NAP1. Our results confirm direct transcriptional inhibition by H1 and establish a gene-specific H1 eviction mechanism through an activator-p300-NAP1-H1 pathway.

Subfields: Immunology, Molecular Biology