Breast Cancer Genetics Group, Discipline of Medicine, University of Adelaide and Hanson Institute, SA Pathology, Adelaide, SA, Australia.
J Cell Biochem. 2011 Oct;112(10):2742-7. doi: 10.1002/jcb.23214.
A significant proportion of transcription factors encoded by the human genome are classical C(2) H(2) zinc finger proteins that regulate gene expression by directly interacting with their cognate DNA binding motifs. We previously showed that one such C(2) H(2) zinc finger DNA binding protein, ZNF652 (zinc finger protein 652), specifically and functionally interacts with CBFA2T3 to repress transcription of genes involved in breast oncogenesis. To identify potential targets by which ZNF652 exerts its putative tumour suppressive function, its promoter-specific cistrome was mapped by ChIP-chip. De novo motif scanning of the ZNF652 binding sites identified a novel ZNF652 recognition motif that closely resembles the previously characterised in vitro binding site, being a 10 nucleotide core of that 13 nucleotide sequence. Genes with ZNF652 binding sites function in diverse cellular pathways, and many are involved in cancer development and progression. Characterisation of the in vivo ZNF652 DNA binding motif and identification of potential ZNF652 target genes are key steps towards elucidating the function(s) of this transcription factor in the normal and malignant breast cell.
人类基因组中编码的转录因子很大一部分是经典的 C(2)H(2)锌指蛋白,它们通过直接与同源 DNA 结合基序相互作用来调节基因表达。我们之前曾表明,这种 C(2)H(2)锌指 DNA 结合蛋白 ZNF652(锌指蛋白 652)特异性和功能性地与 CBFA2T3 相互作用,抑制参与乳腺癌发生的基因的转录。为了确定 ZNF652 发挥其潜在肿瘤抑制功能的潜在靶标,通过 ChIP-chip 绘制了其启动子特异性顺式作用元件图谱。对 ZNF652 结合位点的从头 motif 扫描确定了一个新的 ZNF652 识别 motif,它与先前表征的体外结合位点非常相似,是该 13 个核苷酸序列的 10 个核苷酸核心。具有 ZNF652 结合位点的基因在多种细胞途径中发挥作用,其中许多基因参与癌症的发生和发展。体内 ZNF652 DNA 结合 motif 的特征和潜在 ZNF652 靶基因的鉴定是阐明该转录因子在正常和恶性乳腺细胞中的功能的关键步骤。