Shim Jiwon, Lee Junho
Research Center for Cellulomics, Institute of Molecular Biology and Genetics, School of Biological Sciences, Seoul National University, 56-1 Gwanak-gu, Shillim-dong, Seoul 151-742, Republic of Korea.
Biochem Biophys Res Commun. 2008 Feb 29;367(1):130-6. doi: 10.1016/j.bbrc.2007.12.097. Epub 2007 Dec 26.
During development of Caenorhabditis elegans, expression of the RUNX homolog, rnt-1, is tightly regulated both spatially and temporally. In this study, we investigated the mechanism underlying the temporal regulation of rnt-1. We found that rnt-1 contained evolutionarily conserved consensus RUNX binding sequences within one of its introns, and that RNT-1 bound to these intronic sequences both in vitro and in vivo in the presence of BRO-1, suggesting that RNT-1 together with BRO-1 represses its own transcription. Fine deletion and substitution experiments revealed a binding site within the intron that was critical for rnt-1 regulation. Importantly, we found that the TGFbeta homolog, DBL-1, was required for counteracting the repressive activity of BRO-1 at postembryonic stages. Accordingly, ectopic expression of DBL-1 induced transcription of rnt-1 in the lateral hypodermis and other tissues even at the postembryonic stages. Taken together, our data suggest that rnt-1 expression is regulated by the balance between DBL-1-mediated activation and BRO-1-mediated repression at the postembryonic stages.
在秀丽隐杆线虫的发育过程中，RUNX同源物rnt-1的表达在空间和时间上都受到严格调控。在本研究中，我们探究了rnt-1时间调控的潜在机制。我们发现rnt-1在其一个内含子内含有进化上保守的共有RUNX结合序列，并且在BRO-1存在的情况下，RNT-1在体外和体内均与这些内含子序列结合，这表明RNT-1与BRO-1一起抑制其自身转录。精细的缺失和替换实验揭示了内含子内一个对rnt-1调控至关重要的结合位点。重要的是，我们发现TGFβ同源物DBL-1是在胚胎后期抵消BRO-1抑制活性所必需的。因此，即使在胚胎后期，DBL-1的异位表达也会诱导侧皮下组织和其他组织中rnt-1的转录。综上所述，我们的数据表明，在胚胎后期，rnt-1的表达受DBL-1介导的激活和BRO-1介导的抑制之间平衡的调控。
