The transcriptional repression activity of STAF65γ is facilitated by promoter tethering and nuclear import of class IIa histone deacetylases.
Aberrant expression levels of transcriptional regulators result in alterations in transcriptional control. STAF65γ is a structural subunit of the GCN5 transcriptional co-activator complex. Reports showed that STAF65γ is highly expressed in several human cancer cells, but the consequences of this aberrant expression pattern remain elusive. Here, we show that the STAF65γ protein is highly expressed in lung adenocarcinoma patients and high levels of STAF65γ correlate with poor prognosis. High levels of STAF65γ cause repression of the c-Myc oncogene through physical association with transcription factor YY1 and co-repressors HDACs. Physical interactions between STAF65γ and class IIa HDACs facilitate nuclear enrichment and regulate the assembly of HDAC complexes. Moreover, SUMOylation of STAF65γ is necessary for maintaining the co-repressor complex containing YY1 and class IIa HDACs at the promoter. Our findings reveal a distinct role of STAF65γ in nuclear import, transcriptional repression, and cell cycle regulation at high levels of expression, which is associated with poor clinical outcomes of lung adenocarcinoma.
Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
Feng-Shu
FS
Hsieh
Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
Nai-Tzu
NT
Chen
Department of Biotechnology, Asia University, Taichung 41354, Taiwan.
Ya-Li
YL
Yao
Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
Shi-Yun
SY
Wang
Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
Jeremy J W
JJ
Chen
Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
Chien-Chen
CC
Lai
Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan. Electronic address: yangwm@nchu.edu.tw.
Wen-Ming
WM
Yang
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics; D058207:Sumoylation; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor / Q000235:genetics
D012097:Repressor Proteins; D015534:Trans-Activators; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C114253:ZNF143 protein, human; D006655:Histone Deacetylases
Histone deacetylases; Lung adenocarcinoma; STAF65γ; Transcriptional regulation; YY1