HBO1 HAT complexes target chromatin throughout gene coding regions via multiple PHD finger interactions with histone H3 tail.
The HBO1 HAT protein is the major source of histone H4 acetylation in vivo and has been shown to play critical roles in gene regulation and DNA replication. A distinctive characteristic of HBO1 HAT complexes is the presence of three PHD finger domains in two different subunits: tumor suppressor proteins ING4/5 and JADE1/2/3. Biochemical and functional analyses indicate that these domains interact with histone H3 N-terminal tail region, but with a different specificity toward its methylation status. Their combinatorial action is essential in regulating chromatin binding and substrate specificity of HBO1 complexes, as well as cell growth. Importantly, localization analyses on the human genome indicate that HBO1 complexes are enriched throughout the coding regions of genes, supporting a role in transcription elongation. These results underline the importance and versatility of PHD finger domains in regulating chromatin association and histone modification crosstalk within a single protein complex.
Saksouk
Nehmé
N
Laval University Cancer Research Center, Hôtel-Dieu de Québec (CHUQ), Quebec City, QC, Canada.
Avvakumov
Nikita
N
Champagne
Karen S
KS
Hung
Tiffany
T
Doyon
Yannick
Y
Cayrou
Christelle
C
Paquet
Eric
E
Ullah
Mukta
M
Landry
Anne-Julie
AJ
Côté
Valérie
V
Yang
Xiang-Jiao
XJ
Gozani
Or
O
Kutateladze
Tatiana G
TG
Côté
Jacques
J
D000107:Acetylation; D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D051548:Histone Acetyltransferases