[Bioinformatics scan analysis for predicting drug targeted modulation on ID4 gene expression].
Low expression of ID4 gene is tightly related with carcinogenesis and high expression shows a definite anti-leukemia effect, though little expression in some leukemia cells. The main purpose of this preliminary work was to analyze the construction of ID4 gene promoter and to predict the cis elements in the ID4 promoter region by scanning the drug candidate with bioinformatics method. All these work are the primary part for finding effective drugs in the treatment of leukemia via the way of ID4 expression regulation. According to the data in GenBank and Internet platform, the 5'-untranslated sequence just upstream of ID4 ORF was virtually cloned. TESS, Genomatix and GenBank databank were used to analyze the cis elements in this area. RSA was used to find the distribution patterns for all these possible elements. SAGE and GEO datasets were used to find active substances which have the effect on the ID4 expression. The rsults indicated that ID4 had a type II promoter with a typical TATA box-45 bp upstream the transcriptional original site. There were a lot of various cis elements in the 5'-untranslated region upstream, including both positive element candidates such as Sp1, c-Myb, abaA, GR, ER, Zeste and C/EBPalpha and negative element candidates such as CCAAT-binding factor, GCF, WT1-KTS, HiNF-C and EGR2. It is concluded that estrogen, dexamethasone, thyroid hormone and follicle stimulating hormone may participate in the regulation of ID4 gene expression in both positive and negative manners.
Lu
Xue-Chun
XC
Department of Geriatric Hematology, Department of Hematolody, PLA General Hospital, Beijing 100853, China.
Chi
Xiao-Hua
XH
Lou
Fang-Ding
FD
Zhu
Hong-Li
HL
Fan
Hui
H
Li
Su-Xia
SX
Yu
Li
L
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D019295:Computational Biology / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology; D016503:Drug Delivery Systems; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism*; D007938:Leukemia / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016385:TATA Box / Q000235:genetics*
D020121:5' Untranslated Regions; D004967:Estrogens; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D003907:Dexamethasone; D005640:Follicle Stimulating Hormone