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首页> 美国卫生研究院文献>Molecular and Cellular Biology >Transcriptional regulation of alpha(1b) adrenergic receptors (alpha(1b)AR) by nuclear factor 1 (NF1): a decline in the concentration of NF1 correlates with the downregulation of alpha(1b)AR gene expression in regenerating liver.
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Transcriptional regulation of alpha(1b) adrenergic receptors (alpha(1b)AR) by nuclear factor 1 (NF1): a decline in the concentration of NF1 correlates with the downregulation of alpha(1b)AR gene expression in regenerating liver.

机译：核因子1（NF1）对α（1b）肾上腺素能受体（alpha（1b）AR）的转录调控：NF1浓度的下降与再生肝中alpha（1b）AR基因表达的下调有关。

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The 5' upstream region from --490 to --540 (footprint II) within the dominant P2 promoter of the rat alpha(1b) adrenergic receptor (alpha(1b)AR) gene is recognized by a sequence-specific DNA-binding protein (B. Gao, M. S. Spector, and G. Kunos, J. Biol. Chem. 270:5614-5619, 1995). This protein, detectable in Southwestern (DNA-protein) blots of crude nuclear extracts as 32- and 34-kDa bands, has been purified 6,000-fold from rat livers by DEAE-Sepharose, heparin-Sepharose, and DNA affinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and UV cross-linking of the purified protein indicated the same molecular mass as that in crude extracts. Methylation interference analysis revealed strong contact with a TTGGCT hexamer and weak contact with a TGGCGT hexamer in the 3' and 5' portions of footprint II, respectively. Nucleotide substitutions within these hexamers significantly reduced protein binding to footprint II and the promoter activity of P2 in Hep3B cells. The purified protein also bound to the nuclear factor 1 (NF1)/CTF consensus sequence, albeit with lower affinity. Gel mobility supershift and Western blotting (immunoblotting) analyses using an antibody against the NF1/CTF protein identified the purified 32- and 34-kDa polypeptides as NF1 or a related protein. Cotransfection into Hep3B cells or primary rat hepatocytes of cDNAs of the NF1-like proteins NF1/L, NF1/X, and NF1/Redl resulted in a three- to fivefold increase in transcription directed by wild-type P2 but not by the mutated P2. Partial hepatectomy markedly decreased the levels of NF1 in the remnant liver and its binding to P2, which paralleled declines in the rate of transcription of the alpha(1b)AR gene and in the steady-state levels of its mRNA. These observations indicate that NF1 activates transcription of the rat alpha(1b)AR gene via interacting with its P2 promoter and that a decline in the expression of NF1 is one of the mechanisms responsible for the reduced expression of the alpha(1b)AR gene during liver regeneration.
机译：大鼠alpha（1b）肾上腺素能受体（alpha（1b）AR）基因的显性P2启动子内从--490到--540的5'上游区域（足迹II）被序列特异性DNA结合蛋白识别（B.Gao，MS Spector，和G.Kunos，J.Biol.Chem.270：5614-5619，1995）。该蛋白在粗核提取物的西南（DNA蛋白）印迹中可检测到32 kDa和34 kDa的条带，已通过DEAE-Sepharose，肝素-Sepharose和DNA亲和层析从大鼠肝脏中纯化了6,000倍。十二烷基硫酸钠-聚丙烯酰胺凝胶电泳和纯化蛋白的UV交联表明与粗提取物中的分子量相同。甲基化干扰分析表明，在足迹II的3'和5'部分中，与TTGGCT六聚体的强接触和与TGGCGT六聚体的弱接触。这些六聚体中的核苷酸取代显着降低了蛋白与足迹II的结合以及Hep3B细胞中P2的启动子活性。纯化的蛋白质也与核因子1（NF1）/ CTF共有序列结合，尽管亲和力较低。使用针对NF1 / CTF蛋白的抗体进行的凝胶迁移率超移和Western blotting（免疫印迹）分析确定了纯化的32-kDa和34-kDa多肽为NF1或相关蛋白。 NF1样蛋白NF1 / L，NF1 / X和NF1 / Red1的cDNA共转染到Hep3B细胞或原代大鼠肝细胞中，导致野生型P2而非突变P2导致的转录增加三到五倍。肝部分切除术显着降低了残余肝脏中NF1的水平及其与P2的结合，这与alpha（1b）AR基因的转录速率及其mRNA稳态水平的下降平行。这些观察结果表明，NF1通过与其P2启动子相互作用来激活大鼠alpha（1b）AR基因的转录，并且NF1表达的下降是导致在此过程中alpha（1b）AR基因表达降低的机制之一。肝脏再生。

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