Renal Tubule-specific Transcription and Chromosomal Localization of Rat Thiazide-sensitive Na-Cl Cotransporter Gene*
Renal Tubule-specific Transcription and Chromosomal Localization of Rat Thiazide-sensitive Na-Cl Cotransporter Gene*
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大鼠噻嗪类敏感 Na-Cl 协同转运蛋白基因的肾小管特异性转录和染色体定位*
DOI：
10.1074/jbc.m101614200
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
K. Takeuchi
中科院分区：
文献类型：
--
作者：
Y. Taniyama;Kazunori Sato;A. Sugawara;A. Uruno;Y. Ikeda;M. Kudo;Sadayoshi Ito;K. Takeuchi
研究了噻嗪敏感性钠-氯协同转运蛋白（TSC）基因在肾脏表达定位的分子机制。TSC基因定位于染色体19p12 - 14。在培养的细胞中，大鼠rTSC基因的5 ′侧翼区（5 ′ FL/rTSC）具有组织特异性转录活性，主要启动子区位于− 580和− 141之间。为了进一步研究组织特异性转录，产生了携带LacZ基因上游融合的5 ′ FL/rTSC的转基因大鼠。免疫组化结果显示LacZ基因与TSC共定位于远曲小管（DCT），提示5 ′ FL/rTSC调控肾小管特异性TSC表达。由于转录因子HFH-3（肝细胞核因子-3/folk head homologue-3）也定位于DCT，因此研究了组织特异性转录中HFH-3结合的假定顺式作用元件（HFH-3/rTSC，− 400/− 387位置）的可能作用。缺失和突变分析表明，HFH-3/rTSC的转录实际上是响应于HFH-3，和电泳迁移率变动分析表明，在体外合成的HFH-3的HFH-3/rTSC的直接结合。结论：该基因定位于大鼠染色体19p12 - 24。TSC基因的转录调控区赋予DCT特异性基因表达。DCT特异性转录因子HFH-3可能参与TSC基因的肾小管特异性转录。
The molecular mechanism underlying the renal expression localization of the thiazide-sensitive Na-Cl cotransporter (TSC) gene was studied. TheTSC gene was localized to chromosome 19p12–14. In cultured cells, tissue-specific transcription activity of the 5′-flanking region of the rat rTSC gene (5′FL/rTSC) was demonstrated, and the major promoter region was located between position −580 and −141. To further examine the tissue-specific transcription, transgenic rats harboring the 5′FL/rTSC fused upstream of the LacZ gene were generated. Immunohistochemical analysis clearly showed that LacZ gene expression was co-localized to distal convoluted tubules (DCT) with TSC, indicating that the 5′FL/rTSC regulates the renal tubule-specific TSC expression. Because a transcription factor, HFH-3 (hepatocyte nuclear factor-3/folk head homologue-3), had also been localized to DCT, a possible role of the putative cis-acting element (HFH-3/rTSC, −400/−387 position) for HFH-3 binding in the tissue-specific transcription was examined. Deletion and mutation analyses suggested that transcription of the HFH-3/rTSC was actually responsive to HFH-3, and electrophoretic mobility shift assay showed a direct binding of in vitrosynthesized HFH-3 to the HFH-3/rTSC. In conclusion, therTSC gene is localized to rat chromosome 19p12–24. The transcription regulatory region of the TSC gene confers DCT-specific gene expression. DCT-specific transcription factor HFH-3 may be involved in the renal tubule-specific transcription ofTSC gene.
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三个上皮钠通道亚基基因和一个顶端氯化钠协同转运蛋白基因的小鼠染色体位置。
影响因子：
4.4
作者：
Pathak,BG;ShaughnessyJr,JD;Meneton,P;Greeb,J;Shull,GE;Jenkins,NA;Copeland,NG
通讯作者：
Copeland,NG
影响因子：
20.1
作者：
TAKEUCHI, K;ALEXANDER, RW;MURPHY, TJ
通讯作者：
MURPHY, TJ
噻嗪类敏感的 Na-Cl 协同转运蛋白 rTSC1 在大鼠肾脏中的定位。
影响因子：
19.6
作者：
Plotkin,MD;Kaplan,MR;Verlander,JW;Lee,WS;Brown,D;Poch,E;Gullans,SR;Hebert,SC
通讯作者：
Hebert,SC
钙调节激素对噻嗪类受体密度的影响。
DOI：
10.1681/asn.v771052
发表时间：
1996
期刊：
Journal of the American Society of Nephrology : JASN
影响因子：
--
作者：
Blakely,P;Vaughn,DA;Fanestil,DD
通讯作者：
Fanestil,DD
DOI：
10.1073/pnas.95.24.14552
发表时间：
1998-11-24
影响因子：
11.1
作者：
Kim, GH;Masilamani, S;Knepper, MA
通讯作者：
Knepper, MA