Yasuhiko Yukuto, Hirabayashi Yoko, Ono Ryuichi
Division of Cellular and Molecular Toxicology, Biological Safety Research Centre, National Institute of Health SciencesTokyo, Japan.
Front Chem. 2017 Jun 15;5:34. doi: 10.3389/fchem.2017.00034. eCollection 2017.
Retrotransposons are abundant in mammalian genomes and can modulate the gene expression of surrounding genes by disrupting endogenous binding sites for transcription factors (TFs) or providing novel TFs binding sites within retrotransposon sequences. Here, we show that a (C/T)CACACCT sequence motif in ORR1A, ORR1B, ORR1C, and ORR1D, Long Terminal Repeats (LTRs) of MaLR endogenous retrovirus (ERV), is the direct target of Tbx6, an evolutionary conserved family of T-box TFs. Moreover, by comparing gene expression between control mice (Tbx6 +/-) and Tbx6-deficient mice (Tbx6 -/-), we demonstrate that at least four genes, , and , are down-regulated with Tbx6 deficiency. These results suggest that ORR1A, ORR1B, ORR1C and ORR1D may contribute to the evolution of mammalian embryogenesis.
逆转录转座子在哺乳动物基因组中大量存在，可通过破坏转录因子（TFs）的内源性结合位点或在逆转录转座子序列内提供新的TFs结合位点来调节周围基因的表达。在此，我们表明，MaLR内源性逆转录病毒（ERV）的长末端重复序列（LTRs），即ORR1A、ORR1B、ORR1C和ORR1D中的（C/T）CACACCT序列基序，是T-box转录因子进化保守家族Tbx6的直接靶点。此外，通过比较对照小鼠（Tbx6+/-）和Tbx6缺陷小鼠（Tbx6-/-）之间的基因表达，我们证明至少四个基因， 和 ，在Tbx6缺陷时表达下调。这些结果表明，ORR1A、ORR1B、ORR1C和ORR1D可能有助于哺乳动物胚胎发育的进化。
