Gene-Specific H1 Eviction through a Transcriptional Activator?p300?NAP1?H1 Pathway.
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.
Mesh Terms:
Acetylation, B-Lymphocytes, Binding Sites, CCCTC-Binding Factor, CD40 Antigens, Chromatin, E1A-Associated p300 Protein, Histone Code, Histones, Humans, Molecular Chaperones, Nucleosomes, Promoter Regions, Genetic, Protein Binding, Proteins, Transcription, Genetic, tRNA Methyltransferases
Acetylation, B-Lymphocytes, Binding Sites, CCCTC-Binding Factor, CD40 Antigens, Chromatin, E1A-Associated p300 Protein, Histone Code, Histones, Humans, Molecular Chaperones, Nucleosomes, Promoter Regions, Genetic, Protein Binding, Proteins, Transcription, Genetic, tRNA Methyltransferases
Mol. Cell
Date: Dec. 18, 2018
PubMed ID: 30902546
View in: Pubmed Google Scholar
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