Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity.
Histone acetyltransferases (HATs) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF family of scaffold proteins. Their plant homeodomain (PHD)-Zn knuckle-PHD domain is essential for binding chromatin and is restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1-BRPF1 complex acetylates only H3 in chromatin. We mapped a small region to the N terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity between H4 and H3 tails. These results uncover a crucial new role for associated proteins within HAT complexes, previously thought to be intrinsic to the catalytic subunit.
Laval University Cancer Research Center, Hôtel-Dieu de Québec (CHUQ), Quebec City, Québec G1R 2J6, Canada;
Marie-Eve
ME
Lalonde
Nikita
N
Avvakumov
Karen C
KC
Glass
France-Hélène
FH
Joncas
Nehmé
N
Saksouk
Michael
M
Holliday
Eric
E
Paquet
Kezhi
K
Yan
Qiong
Q
Tong
Brianna J
BJ
Klein
Song
S
Tan
Xiang-Jiao
XJ
Yang
Tatiana G
TG
Kutateladze
Jacques
J
Côté
D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
D048868:Adaptor Proteins, Signal Transducing; D002843:Chromatin; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D011994:Recombinant Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C086011:BRPF1 protein, human; D000092468:Bromodomain Containing Proteins; C508131:ING5 protein, human; C469360:JADE1 protein, human; C496553:KAT7 protein, human
BRPF1; MYST family; PHD fingers; acetyltransferase complexes; chromatin acetylation; histone tails