Ren Guoling, Zhang Guocui, Dong Zhixiong, Liu Zhiwei, Li Lin, Feng Yunpeng, Su Dongmei, Zhang Yu, Huang Baiqu, Lu Jun
Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, PR China.
Int J Biochem Cell Biol. 2009 May;41(5):1094-101. doi: 10.1016/j.biocel.2008.10.015. Epub 2008 Nov 1.
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.
HOXB13是一种同源结构域蛋白，被认为在雄激素受体（AR）阴性前列腺癌细胞的生长停滞中发挥作用。HOXB13的表达仅限于表达AR的前列腺细胞。在本报告中，我们证明组蛋白去乙酰化酶抑制剂丁酸钠（NaB）能够诱导AR阴性前列腺癌细胞的细胞生长停滞并增加HOXB13的表达。我们还表明，组蛋白去乙酰化酶4（HDAC4）和YY1均通过涉及组蛋白乙酰化修饰的表观遗传机制参与HOXB13表达的抑制。具体而言，免疫共沉淀试验表明HDAC4和YY1形成了复合物。染色质免疫沉淀（ChIP）试验证实YY1将HDAC4募集到HOXB13启动子上。此外，启动子截短和点突变研究确定HOXB13启动子上的两个近端YY1结合位点对于YY1和HDAC4的募集至关重要。本报告中的数据表明，YY1和HDAC4通过组蛋白的表观遗传修饰抑制HOXB13的转录调控来影响细胞生长。
