PMID- 10452946 OWN - NLM STAT- MEDLINE DCOM- 19990923 LR - 20211203 IS - 0378-1119 (Print) IS - 0378-1119 (Linking) VI - 236 IP - 2 DP - 1999 Aug 20 TI - Cloning and characterization of the alternative promoter regions of the human LIMK2 gene responsible for alternative transcripts with tissue-specific expression. PG - 259-71 AB - We previously isolated the human LIMK2 gene and identified two alternative transcripts, LIMK2a and LIMK2b, which were differentially regulated in a tissue-specific manner. To examine this differential tissue-specific expression in detail, an RNase protection assay was performed, which demonstrated three expression patterns of the LIMK2 isoforms. In digestive organs, the LIMK2a transcripts were preferentially expressed in fetal and adult tissues; in brain and lung, the LIMK2a transcript was predominantly expressed only in fetal tissue, and in placenta, the LIMK2b transcript was expressed more abundantly than that of LIMK2a. To further investigate this mechanism and the transcription factors involved, we isolated the two distinct 5' upstream regions from the phage genomic library and found that both LIMK2a and 2b promoters have a single major transcription initiation site and the characteristics of a TATA-less promoter. A luciferase reporter assay of the transcriptional activity revealed positive as well as negative regulatory regions within both promoters. The co-transfection assay suggested that the MZF-1 might regulate the expression of the LIMK2 isoforms in a different manner. The RORalpha1 might also be involved in the transcriptional regulation of the LIMK2b isoform. The genomic structure of the LIMK2 gene was also determined. These findings should lead to a better understanding of the possibly diverse functions of the LIMK family. FAU - Nomoto, S AU - Nomoto S AD - Laboratory of Ultrastructure Research, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. FAU - Tatematsu, Y AU - Tatematsu Y FAU - Takahashi, T AU - Takahashi T FAU - Osada, H AU - Osada H LA - eng SI - GENBANK/AB016655 SI - GENBANK/AB016656 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Gene JT - Gene JID - 7706761 RN - 0 (DNA-Binding Proteins) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (MZF1 protein, human) RN - 0 (Nuclear Receptor Subfamily 1, Group F, Member 1) RN - 0 (Protein Isoforms) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - EC 2.7.11.1 (LIMK2 protein, human) RN - EC 2.7.11.1 (Lim Kinases) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - *Alternative Splicing MH - Base Sequence MH - Cloning, Molecular MH - DNA-Binding Proteins/*genetics MH - Gene Expression Regulation MH - Gene Library MH - Genes, Reporter MH - Humans MH - Kruppel-Like Transcription Factors MH - Lim Kinases MH - Models, Genetic MH - Molecular Sequence Data MH - Nuclear Receptor Subfamily 1, Group F, Member 1 MH - Organ Specificity MH - Placenta/metabolism MH - *Promoter Regions, Genetic MH - Protein Isoforms MH - Protein Serine-Threonine Kinases MH - Receptors, Cytoplasmic and Nuclear/genetics MH - Regulatory Sequences, Nucleic Acid MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tissue Distribution MH - Trans-Activators/genetics MH - Transcription Factors/genetics MH - Transcription, Genetic MH - Transcriptional Activation MH - Tumor Cells, Cultured EDAT- 1999/08/24 00:00 MHDA- 1999/08/24 00:01 CRDT- 1999/08/24 00:00 PHST- 1999/08/24 00:00 [pubmed] PHST- 1999/08/24 00:01 [medline] PHST- 1999/08/24 00:00 [entrez] AID - S0378111999002802 [pii] AID - 10.1016/s0378-1119(99)00280-2 [doi] PST - ppublish SO - Gene. 1999 Aug 20;236(2):259-71. doi: 10.1016/s0378-1119(99)00280-2.