Gene-Specific H1 Eviction through a Transcriptional Activator→p300→NAP1→H1 Pathway

Miho Shimada; Wei-Yi Chen; Tomoyoshi Nakadai; Takashi Onikubo; Mohamed Guermah; Daniela Rhodes; Robert G Roeder

doi:10.1016/j.molcel.2019.02.016

Gene-Specific H1 Eviction through a Transcriptional Activator→p300→NAP1→H1 Pathway

Mol Cell. 2019 Apr 18;74(2):268-283.e5. doi: 10.1016/j.molcel.2019.02.016. Epub 2019 Mar 19.

Authors

Miho Shimada¹, Wei-Yi Chen², Tomoyoshi Nakadai¹, Takashi Onikubo¹, Mohamed Guermah¹, Daniela Rhodes³, Robert G Roeder⁴

Affiliations

¹ Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
² Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan; Cancer Progression Research Center, National Yang-Ming University, Taipei 112, Taiwan.
³ NTU Institute of Structural Biology and School of Biological Sciences, Nanyang Technological University, Singapore 636921, Singapore.
⁴ Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA. Electronic address: roeder@rockefeller.edu.

Abstract

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.

Keywords: B cell maturation; CTCF; NAP1; NF-κB; higher-order chromatin; in vitro transcription; linker histone; p300; transcription.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acetylation
B-Lymphocytes / chemistry
Binding Sites
CCCTC-Binding Factor / chemistry
CCCTC-Binding Factor / genetics*
CD40 Antigens / genetics
Chromatin / chemistry
Chromatin / genetics
E1A-Associated p300 Protein / chemistry
E1A-Associated p300 Protein / genetics*
Histone Code
Histones / chemistry
Histones / genetics
Humans
Molecular Chaperones / chemistry
Molecular Chaperones / genetics
Nucleosomes / chemistry
Nucleosomes / genetics
Promoter Regions, Genetic
Protein Binding / genetics
Proteins / chemistry
Proteins / genetics*
Transcription, Genetic*
tRNA Methyltransferases

Substances

CCCTC-Binding Factor
CD40 Antigens
Chromatin
Histones
Molecular Chaperones
Nucleosomes
Proteins
TRMO protein, human
tRNA Methyltransferases
E1A-Associated p300 Protein
EP300 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding