ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation.
Members of the ING family of tumor suppressors regulate cell cycle progression, apoptosis, and DNA repair as important cofactors of p53. ING1 and ING3 are stable components of the mSin3A HDAC and Tip60/NuA4 HAT complexes, respectively. We now report the purification of the three remaining human ING proteins. While ING2 is in an HDAC complex similar to ING1, ING4 associates with the HBO1 HAT required for normal progression through S phase and the majority of histone H4 acetylation in vivo. ING5 fractionates with two distinct complexes containing HBO1 or nucleosomal H3-specific MOZ/MORF HATs. These ING5 HAT complexes interact with the MCM helicase and are essential for DNA replication to occur during S phase. Our data also indicate that ING subunits are crucial for acetylation of chromatin substrates. Since INGs, HBO1, and MOZ/MORF contribute to oncogenic transformation, the multisubunit assemblies characterized here underscore the critical role of epigenetic regulation in cancer development.
Doyon
Yannick
Y
Laval University Cancer Research Center, Hôtel-Dieu de Québec (CHUQ), Québec City, Québec G1R 2J6, Canada.
Cayrou
Christelle
C
Ullah
Mukta
M
Landry
Anne-Julie
AJ
Côté
Valérie
V
Selleck
William
W
Lane
William S
WS
Tan
Song
S
Yang
Xiang-Jiao
XJ
Côté
Jacques
J
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D004261:DNA Replication; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000074443:Lysine Acetyltransferase 5; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015534:Trans-Activators / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D018398:Homeodomain Proteins; C501503:ING1 protein, human; C444654:ING2 protein, human; C459806:ING3 protein, human; C483230:ING4 protein, human; C508131:ING5 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; C108712:KAT6A protein, human; C487137:KAT6B protein, human; C496553:KAT7 protein, human; D000074443:Lysine Acetyltransferase 5; D056264:Sin3 Histone Deacetylase and Corepressor Complex