Eaf5/7/3 form a functionally independent NuA4 submodule linked to RNA polymerase II-coupled nucleosome recycling.
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.
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.
Dorine
D
Rossetto
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.
Myriam
M
Cramet
Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada.
Alice Y
AY
Wang
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.
Anne-Lise
AL
Steunou
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.
Nicolas
N
Lacoste
Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada.
Julia M
JM
Schulze
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.
Valérie
V
Côté
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.
Julie
J
Monnet-Saksouk
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.
Sandra
S
Piquet
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.
Amine
A
Nourani
Center for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, BC, Canada.
Michael S
MS
Kobor
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.
Jacques
J
Côté
D000123:Acetyltransferases / Q000378:metabolism; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D051548:Histone Acetyltransferases / Q000378:metabolism*; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009707:Nucleosomes / Q000502:physiology*; D012319:RNA Polymerase II / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D046912:Multiprotein Complexes; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C428131:Eaf3 protein, S cerevisiae; C528251:Eaf5 protein, S cerevisiae; C528253:Eaf7 protein, S cerevisiae; D051548:Histone Acetyltransferases; C504740:NuA4 protein, S cerevisiae; D012319:RNA Polymerase II
NuA4; histone acetylation; nucleosome dynamics; transcription elongation