SAFB1, an RBMX-binding protein, is a newly identified regulator of hepatic SREBP-1c gene.
SAFB1, an RBMX-binding protein, is a newly identified regulator of hepatic SREBP-1c gene.
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DOI：
10.5483/bmbrep.2009.42.4.232
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发表时间：
2009-04
期刊：
影响因子：
3.8
通讯作者：
Yasushi Omura;Y. Nishio;T. Takemoto;Chikako Ikeuchi;Osamu Sekine;K. Morino;Y. Maeno;T. Obata;S. Ugi;H. Maegawa;H. Kimura;A. Kashiwagi
中科院分区：
文献类型：
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作者：
Yasushi Omura;Y. Nishio;T. Takemoto;Chikako Ikeuchi;Osamu Sekine;K. Morino;Y. Maeno;T. Obata;S. Ugi;H. Maegawa;H. Kimura;A. Kashiwagi
固醇调节元件结合蛋白(SREBP)-1c在肝脏中的造脂酶的调节中起着关键作用。我们先前报道了一个X染色体连锁的RNA结合基序(RBMX)调节SREBP-1c的启动子活性。然而，它是如何调控基因表达的，仍然是未知的。为了阐明这一机制，我们以RBMX为诱饵，采用酵母双杂交技术，从小鼠肝脏中筛选出了一个新的文库，并鉴定出了支架附着因子B1(SCFF1)。免疫沉淀实验证实SAFB1与RBMX结合。染色质免疫沉淀实验显示SAFB1和RBMX均与SREBP-1c基因上游区域结合。Safb1的RNA干扰降低了基础启动子和RBMX诱导的SREBP-1c启动子活性，导致SREBP-1c基因表达下降。只有在RBMX存在的情况下，才能发现SAFB1过表达对SREBP-1c启动子的影响。这些结果表明SAFB1通过与RBMX的相互作用在SREBP-1c的激活中发挥主要作用。
Sterol regulatory element-binding protein (SREBP)-1c plays a crucial role in the regulation of lipogenic enzymes in the liver. We previously reported that an X-chromosome-linked RNA binding motif (RBMX) regulates the promoter activity of Srebp-1c. However, still unknown was how it regulates the gene expression. To elucidate this mechanism, we screened the cDNA library from mouse liver by yeast two-hybrid assay using RBMX as bait and identified scaffold attachment factor B1 (SAFB1). Immunoprecipitation assay demonstrated binding of SAFB1 to RBMX. Chromatin immunoprecipitation assay showed binding of both SAFB1 and RBMX to the upstream region of Srebp-1c gene. RNA interference of Safb1 reduced the basal and RBMX-induced Srebp-1c promoter activities, resulting in reduced Srebp-1c gene expression. The effect of SAFB1 overexpression on Srebp-1c promoter was found only in the presence of RBMX. These results indicate a major role for SAFB1 in the activation of Srebp-1c through its interaction with RBMX.