Recruitment of HDAC4 by transcription factor YY1 represses HOXB13 to affect cell growth in AR-negative prostate cancers.
HOXB13 is a homeodomain protein implicated to play a role in growth arrest in AR (androgen receptor)-negative prostate cancer cells. Expression of HOXB13 is restricted to the AR-expressing prostate cells. In this report, we demonstrate that the HDAC inhibitor NaB (sodium butyrate) was able to induce cell growth arrest and to increase HOXB13 expression in AR-negative prostate cancer cells. We also show that both HDAC4 and YY1 participated in the repression of HOXB13 expression through an epigenetic mechanism involving histone acetylation modification. Specifically, co-immunoprecipitation assays revealed that HDAC4 and YY1 formed a complex. The chromatin immunoprecipitation (ChIP) assays verified that HDAC4 was recruited to HOXB13 promoter by YY1. Moreover, promoter truncation and point mutation studies determined that the two proximal YY1 binding sites on the HOXB13 promoter were essential for the recruitments of YY1 and HDAC4. Data presented in this report suggest that YY1 and HDAC4 affected cell growth by repressing transcriptional regulation of HOXB13 through an epigenetic modification of histones.
Ren
Guoling
G
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, PR China.
Zhang
Guocui
G
Dong
Zhixiong
Z
Liu
Zhiwei
Z
Li
Lin
L
Feng
Yunpeng
Y
Su
Dongmei
D
Zhang
Yu
Y
Huang
Baiqu
B
Lu
Jun
J
D000107:Acetylation; D001665:Binding Sites; D002087:Butyrates / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D002087:Butyrates; C484414:HOXB13 protein, human; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D018398:Homeodomain Proteins; D011944:Receptors, Androgen; D012097:Repressor Proteins; D050986:YY1 Transcription Factor; C400300:HDAC4 protein, human; D006655:Histone Deacetylases