Comput Biol Chem - Identification of virtual signal transducers and activators of transcription response elements in the human insulin receptor gene promoter.

Tópicos

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Resumo

In this study, we look for the existence of signal transducers and activators of transcription response elements (STATREs) in the human insulin receptor (hIR) gene promoter and their possible relation with the estradiol-provoked transcriptional repression of the hIR gene and cellular insulin resistance in U-937 human promonocytic cells. Potential STATREs in the region from -1819 to -271 bp of the hIR gene promoter were identified by their homology with the consensus STATRE (5'TTCnnnGAA3') using the SEQFIND programme developed in our laboratory. We located five virtual STATRE-like sites: [(I): -1472/-1464], [(II): -1548/-1540], [(III): -1552/-1544], [(IV): -1587/-1579] and [(V): -1678/-1670] showing a difference of only one base from this consensus. These STATREs-like sites were situated between 33 bp upstream the 5' half-element of the estrogen response element 1 (ERE1)-like (-1430/-1418) and 102 bp upstream the 5' half-element of the ERE2-like (-1567/-1555) complexed with AP-1-like sites. A principal complex constituted by STATREs (II-IV) the ERE2 and AP-1 sites (IV and V) was located between -1587/-1540 bp of the hIR gene promoter. In conclusion, these results represent the first identification of virtual STATREs in the hIR gene promoter. These STATREs appear to be specifically located in the surroundings of the two EREs overlapped by various AP-1 sites. These complexes could mediate crosstalk among STATs, estrogen receptor ? (ER?), and AP-1 regulating the ER?-mediated transcriptional repression of the hIR gene and insulin resistance in U-937 cells.

Resumo Limpo

studi look exist signal transduc activ transcript respons element statr human insulin receptor hir gene promot possibl relat estradiolprovok transcript repress hir gene cellular insulin resist u human promonocyt cell potenti statr region bp hir gene promot identifi homolog consensus statr ttcnnngaa use seqfind programm develop laboratori locat five virtual statrelik site ii iii iv v show differ one base consensus statreslik site situat bp upstream halfel estrogen respons element erelik bp upstream halfel erelik complex aplik site princip complex constitut statr iiiv ere ap site iv v locat bp hir gene promot conclus result repres first identif virtual statr hir gene promot statr appear specif locat surround two ere overlap various ap site complex mediat crosstalk among stat estrogen receptor er ap regul ermedi transcript repress hir gene insulin resist u cell

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