Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system
Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system
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DOI：
10.1074/jbc.275.9.6381
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发表时间：
2000-03-03
影响因子：
4.8
通讯作者：
Lee, ME
中科院分区：
文献类型：
--
作者：
Chin, MT;Maemura, K;Lee, ME
我们在酵母双杂交筛选中克隆了一个与芳烃受体核转运子（ARNT）相互作用的心血管限制性基本螺旋-环-螺旋因子。心血管螺旋-环-螺旋因子1 （CHF1）与毛状转录抑制因子家族有远亲关系，我们分析了其在小鼠胚胎发育过程中的表达模式。在第8.5天，CHF1首先在原始心管的原始心室中被检测到，并在整个妊娠期间持续表达。在大鼠心脏中，CHF1的表达在出生后下调，与心肌细胞的终末分化同时发生。在发育中的血管中，CHF1在第9.0天首先出现在背主动脉中，早于报道的平滑肌细胞标记物的表达，并持续到成年。在体外平滑肌细胞分化系统中，CHF1 mRNA在未分化细胞中几乎检测不到，但在分化的平滑肌细胞中却被高度诱导。为了确定CHF1是否可能影响ARNT的功能，我们进行了转染研究，CHF1共转染抑制了85%的ARNT/ epas1依赖性转录，这种抑制作用是剂量依赖性的。在电泳迁移率研究中，CHF1抑制了ARNT/EPAS1异源二聚体与其靶位点的结合。我们的数据表明CHF1作为一种转录抑制因子，可能在心血管发展中发挥重要作用。
We have cloned a cardiovascular-restricted basic helix-loop-helix factor that interacts with arylhydrocarbon receptor nuclear translocator (ARNT) in a yeast two-hybrid screen. Cardiovascular helix-loop-helix factor 1 (CHF1) is distantly related to the hairy family of transcriptional repressors, We analyzed its expression pattern during mouse embryo development. At day 8.5, the expression of CHF1 is first detected in the primitive ventricle of the primordial heart tube and persists throughout gestation. In rat hearts, this expression is down-regulated after birth, concurrent with terminal differentiation of cardiomyocytes, In the developing vasculature, CHF1 first appears in the dorsal aorta at day 9.0, which precedes the reported expression of smooth muscle cell markers, and persists into adulthood. In an in vitro system of smooth muscle cell differentiation, CHF1 mRNA was barely detectable in undifferentiated cells but was induced highly in differentiated smooth muscle cells, To determine whether CHF1 might affect the function of ARNT, we performed transfection studies, Co-transfection of CHF1 inhibited ARNT/EPAS1-dependent transcription by 85% and this inhibition is dose-dependent. In electrophoretic mobility studies, CHF1 inhibited the binding of the ARNT/EPAS1 heterodimer to its target site. Our data suggest that CHF1 functions as a transcriptional repressor and may play an important role in cardiovascular development.