The Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, United States.
Biochem Biophys Res Commun. 2011 Jul 22;411(1):115-20. doi: 10.1016/j.bbrc.2011.06.107. Epub 2011 Jun 23.
RUNX1 is a critical transcription factor during embryogenesis and neoplastic disease. To identify novel transcriptional targets of RUNX1 in the context of chromatin, we performed genome wide location analysis (ChIP-on-chip). Here we report that SERPINB13, a gene downregulated in head and neck cancers, is a novel RUNX1transcriptional target. RUNX1 binds the SERPINB13 promoter in chromatin to repress its transcription. Mutation of either RUNX1 binding site in the SERPINB13 promoter increased the activity of the promoter. Finally, overexpression of RUNX1 and concomitant decrease in SERPINB13 expression led to increased activity of cathepsin K, an enzyme inhibited by SERPINB13. These data demonstrate that RUNX1 is an important regulator of SERPINB13 and cathepsin K activity.
RUNX1 是胚胎发生和肿瘤性疾病过程中的关键转录因子。为了鉴定 RUNX1 在染色质背景下的新的转录靶标，我们进行了全基因组定位分析（ChIP-on-chip）。在此，我们报告丝氨酸蛋白酶抑制剂 B13（SERPINB13）是一种新的 RUNX1 转录靶标，它在头颈部癌症中下调。RUNX1 在染色质上结合 SERPINB13 启动子以抑制其转录。SERPINB13 启动子中 RUNX1 结合位点的突变增加了启动子的活性。最后，RUNX1 的过表达和 SERPINB13 表达的同时降低导致组织蛋白酶 K 活性增加，该酶被 SERPINB13 抑制。这些数据表明 RUNX1 是 SERPINB13 和组织蛋白酶 K 活性的重要调节因子。
