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EMBO J. 2014 Jun 17;33(12):1397-415. doi: 10.15252/embj.201386433. Epub 2014 May 19.

Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II-coupled nucleosome recycling.

Author information

1
St-Patrick Research Group in Basic Oncology, Laval University Cancer Research Center Centre de Recherche du CHU de Québec-Axe Oncologie Hôtel-Dieu de Québec, Quebec City, QC, Canada.
2
Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada.
3
St-Patrick Research Group in Basic Oncology, Laval University Cancer Research Center Centre de Recherche du CHU de Québec-Axe Oncologie Hôtel-Dieu de Québec, Quebec City, QC, Canada Jacques.Cote@crhdq.ulaval.ca.

Abstract

The NuA4 histone acetyltransferase complex is required for gene regulation, cell cycle progression, and DNA repair. Dissection of the 13-subunit complex reveals that the Eaf7 subunit bridges Eaf5 with Eaf3, a H3K36me3-binding chromodomain protein, and this Eaf5/7/3 trimer is anchored to NuA4 through Eaf5. This trimeric subcomplex represents a functional module, and a large portion exists in a native form outside the NuA4 complex. Gene-specific and genome-wide location analyses indicate that Eaf5/7/3 correlates with transcription activity and is enriched over the coding region. In agreement with a role in transcription elongation, the Eaf5/7/3 trimer interacts with phosphorylated RNA polymerase II and helps its progression. Loss of Eaf5/7/3 partially suppresses intragenic cryptic transcription arising in set2 mutants, supporting a role in nucleosome destabilization. On the other hand, loss of the trimer leads to an increase of replication-independent histone exchange over the coding region of transcribed genes. Taken together, these results lead to a model where Eaf5/7/3 associates with elongating polymerase to promote the disruption of nucleosomes in its path, but also their refolding in its wake.

KEYWORDS:

NuA4; histone acetylation; nucleosome dynamics; transcription elongation

PMID:
24843044
PMCID:
PMC4194127
DOI:
10.15252/embj.201386433
[Indexed for MEDLINE]
Free PMC Article

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