Opposite role of yeast ING family members in p53-dependent transcriptional activation.
The inhibitor-of-growth (ING) family of proteins was founded by human ING1, a tumor suppressor interacting with p53 in vivo and required for its function in transcription/apoptosis. There are five different ING genes in humans, three of which have been linked to p53 function. In this study, we analyzed the three ING family members present in yeast. We demonstrate that each one is purified as a key component of a specific histone-modifying complex. Pho23 is part of Rpd3/Sin3 histone deacetylase complex, while Yng1 and Yng2 are subunits of the NuA3 and NuA4 histone acetyltransferase complexes, respectively. We also show that the three different ING proteins have opposite roles in transcriptional activation by p53 in vivo. These effects are linked to the presence of each ING in its respective chromatin modifying complex, since mutation of the corresponding catalytic subunit gave similar results. Depletion of Pho23/Rpd3 leads to increased p53-dependent transcription in vivo while depletion of Yng2 abrogates it. Surprisingly, deletion of YNG1 or SAS3 leads to increased transcriptional activation by p53. These data suggest that the NuA3 complex can function in gene-specific repression, an unusual role for a histone acetyltransferase complex. They also demonstrate the key specific role of ING proteins in different chromatin modifying complexes and their opposite functions in p53-dependent transcription.
Nourani
Amine
A
Laval University Cancer Research Center, Hôtel-Dieu de Québec (CHUQ), Quebec City, Quebec G1R 2J6, Canada.
Howe
LeAnn
L
Pray-Grant
Marilyn G
MG
Workman
Jerry L
JL
Grant
Patrick A
PA
Côté
Jacques
J
D000123:Acetyltransferases; D015152:Blotting, Northern; D002843:Chromatin / Q000378:metabolism; D017353:Gene Deletion; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology*
D002843:Chromatin; D009687:Nuclear Proteins; C432409:Pho23 protein, S cerevisiae; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D016159:Tumor Suppressor Protein p53; D000123:Acetyltransferases; C469780:Yng2 protein, S cerevisiae; D051548:Histone Acetyltransferases; C459900:Yng1 protein, S cerevisiae; D006655:Histone Deacetylases