Serial analysis of chromatin occupancy identifies β-catenin target genes in colorectal carcinoma cells
Serial analysis of chromatin occupancy identifies β-catenin target genes in colorectal carcinoma cells
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DOI：
10.1073/pnas.0611576104
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发表时间：
2007-02-27
影响因子：
11.1
通讯作者：
Goodman, Richard H.
中科院分区：
文献类型：
--
作者：
Yochum, Gregory S.;McWeeney, Shannon;Goodman, Richard H.
结直肠癌的大多数情况是由于Writ信号通路的异常，导致β-连环蛋白的核积累。β-连环蛋白主要通过与转录因子的T细胞因子/淋巴增强子结合因子（TCF/Lef）家族结合来激活靶基因的转录。在这份报告中，我们使用染色质占有率系列分析（SACO）来鉴定HCT 116结肠直肠癌细胞中的412个高置信度的β-连环蛋白靶点。在这些靶点中，84%含有共有的TCIF基序，并且在体内被TCF 4占据。在每个共识的侧翼5-bp残基的检查发现在相邻的网站的基序特异性富集。β-Catenin结合定位于蛋白质编码基因的5 '启动子、内部区域和3' IUTR。此外，经典Writ通路的15个组分被鉴定为β-连环蛋白靶基因，表明前馈和反馈机制存在于结肠癌细胞中以调节Writ信号。
Most instances of colorectal cancer are due to abnormalities in the Writ signaling pathway, resulting in nuclear accumulation of beta-catenin. beta-Catenin activates transcription of target genes primarily by associating with the T cell factor/lymphoid enhancerbinding factor (TCF/Lef) family of transcription factors. In this report, we use serial analysis of chromatin occupancy (SACO) to identify412 high-confidence beta-catenin targets in HCT116 colorectal carcinoma cells. Of these targets, 84% contained a consensus TCIF motif and were occupied by TCF4 in vivo. Examination of the flanking 5-bp residues in each consensus revealed motif-specific enrichment at neighboring sites. beta-Catenin binding was localized tothe 5'promoters, internal regions, and 3' IUTRs of protein-coding genes. Furthermore, 15 components of the canonical Writ pathway were identified as beta-catenin target genes, suggesting that feedforward and feedback mechanisms exist to modulate the Writ signal in colon cancer cells.