PMID- 19957534 OWN - NLM STAT- MEDLINE DCOM- 20100202 LR - 20151006 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 89 IP - 24 DP - 2009 Jun 23 TI - [Experimental identification of drugs with function of targeted up-regulating ID4 expression: bioinformatics-based prediction and preliminary validation]. PG - 1714-6 AB - OBJECTIVE: To screen new candidate molecular-targeted anti-leukemia compounds with potential functions of targeted up-regulating ID4 gene expression. METHODS: Promoter region of ID4 gene including the upstream - 3000 bp sequence of transcriptional start site and message RNA sequence were fished out. Online promoter analysis tools of TESS and Genomax were used to search possible sequence of transcriptional start site and message RNA sequence were fished out. Online promoter analysis tools of TESS and Genomax were used to search possible cis-acting structure from human transcription factor database. The activity of related drugs with potential effects upon ID4 gene expression was analyzed using SAGE database. GEO database was applied to search the gene expression profiling regulated by ID4 gene. Finally, similar analysis between gene expression profiling by ID4 and genome-wide profiling regulated by 163 known drugs or active compounds was manipulated to screen the drugs and candidate compounds with similar gene expression profiling with ID4 gene. MOLT4 cell line was treated with the above candidate active compounds to investigate the ID4 gene expression by RT-PCR assay. RESULTS: ID4 gene had a type II promoter with a typical TATA box in upstream -45 bp of transcription start site. The 1300 bp-length promoter of ID4 gene contained a few cis-acting structures classified into two function types, i. e. positive regulatory type, including transcription factors Spl and c-Myb, cAMP, glucocorticoid receptor (GR) and estrogen receptor (ER), and negative regulatory type, including Wilms tumor-1 (WT1) and early growth response-2 (EGR2). The similarity of gene expression profiling was identified between cAMP and ID4 gene. ID4 gene expression was induced in MOLT4 cell line after treatment with calcium dibutyryladenosine cyclophosphate at the concentration of 0.1 mmol/L. CONCLUSION: The comprehensive bioinformatic analysis, based upon the combination of regulatory sequence prediction of promoter, similarity analysis of gene expression profiling and literature review, can be considered as a practical tool in screening the candidate drugs with the activity of targeted regulating functional genes. Calcium dibutyryladenosine cyclophosphate can induce ID4 gene expression in leukemic cells. FAU - Yang, Bo AU - Yang B AD - Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing 100853, China. FAU - Lu, Xue-Chun AU - Lu XC FAU - Liu, Li-Hong AU - Liu LH FAU - Zhu, Hong-Li AU - Zhu HL FAU - Chi, Xiao-Hua AU - Chi XH FAU - Yao, Shan-Qian AU - Yao SQ FAU - Lou, Fang-Ding AU - Lou FD FAU - Yu, Li AU - Yu L LA - chi PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 0 (ID4 protein, human) RN - 0 (Inhibitor of Differentiation Proteins) RN - 0 (RNA, Messenger) SB - IM MH - Cell Line, Tumor MH - *Computational Biology MH - Humans MH - Inhibitor of Differentiation Proteins/*genetics MH - RNA, Messenger/genetics MH - Regulatory Sequences, Nucleic Acid MH - Sequence Analysis, DNA MH - Up-Regulation EDAT- 2009/12/05 06:00 MHDA- 2010/02/03 06:00 CRDT- 2009/12/05 06:00 PHST- 2009/12/05 06:00 [entrez] PHST- 2009/12/05 06:00 [pubmed] PHST- 2010/02/03 06:00 [medline] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2009 Jun 23;89(24):1714-6.