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Gene-Specific H1 Eviction through a Transcriptional Activator→p300→NAP1→H1 Pathway
- Shimada, Miho, Chen, Wei-Yi, Nakadai, Tomoyoshi, Onikubo, Takashi, Guermah, Mohamed, Rhodes, Daniela, Roeder, Robert G.
- Molecular cell 2019 v.74 no.2 pp. 268-283.e5
- B-lymphocytes, acetylation, chromatin, gene activation, genes, histones, transcription (genetics)
- 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 the 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-H1 interactions, is propagated over a CCCTC-binding factor (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.