PMID- 9199934 OWN - NLM STAT- MEDLINE DCOM- 19970915 LR - 20190606 IS - 1088-9051 (Print) IS - 1088-9051 (Linking) VI - 7 IP - 6 DP - 1997 Jun TI - Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the Down syndrome chromosomal region. PG - 615-24 AB - As part of our effort to clone genes of human chromosome 21 that may contribute to Down syndrome, we have previously isolated four exons with homology to Drosophila single-minded (sim) gene, which encodes a transcription factor that is a master regulator of fruit fly neurogenesis. These exons were used to clone and characterize two human homologs of the Drosophila sim gene, SIM1 and SIM2, which map to chromosomes 6q16.3-q21 and 21q22.2, respectively; SIM2 maps within the so-called Down syndrome chromosomal region. Recently, two mouse homologs, Sim1 and Sim2, also have been identified. There is a high level of homology among human, mouse, and Drosophila sim genes in their amino-terminal half where the conserved bHLH, PAS1, PAS2, and HST domains are present. In contrast, the carboxy-terminal parts are only homologous between SIM1 and Sim1 and SIM2 and Sim2. Two isoforms (SIM2 and SIM2s) of human SIM2 have been detected that differ in their 3' ends. Northern blot analysis revealed one mRNA SIM1 species of approximately 9.5 kb and four different mRNA SIM2 species of 2.7, 3, 4.4, and 6 kb in human fetal kidney. The function of both human SIM1 and SIM2 is unknown. However, three copies of SIM2 may contribute to some specific Down syndrome phenotypes because of (1) mapping position, (2) potential function as transcriptional repressor, (3) likely dimerization with other transcription factors, (4) the temporal and spatial expression pattern of mouse Sim2, and (5) the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis. FAU - Chrast, R AU - Chrast R FAU - Scott, H S AU - Scott HS FAU - Chen, H AU - Chen H FAU - Kudoh, J AU - Kudoh J FAU - Rossier, C AU - Rossier C FAU - Minoshima, S AU - Minoshima S FAU - Wang, Y AU - Wang Y FAU - Shimizu, N AU - Shimizu N FAU - Antonarakis, S E AU - Antonarakis SE LA - eng SI - GENBANK/AB003185 SI - GENBANK/U70212 SI - GENBANK/U80456 SI - GENBANK/U80457 PT - Letter PT - Research Support, Non-U.S. Gov't PL - United States TA - Genome Res JT - Genome research JID - 9518021 RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (DNA-Binding Proteins) RN - 0 (Drosophila Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Repressor Proteins) RN - 0 (SIM1 protein, human) RN - 0 (SIM2 protein, human) RN - 0 (sim protein, Drosophila) SB - IM MH - Amino Acid Sequence MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors MH - Chromosome Mapping MH - *Chromosomes, Human, Pair 21 MH - *Chromosomes, Human, Pair 6 MH - Cloning, Molecular MH - DNA-Binding Proteins/*genetics MH - Down Syndrome/*genetics MH - Drosophila/genetics MH - Drosophila Proteins MH - Humans MH - Mice MH - Molecular Sequence Data MH - Nuclear Proteins/*genetics MH - Polymerase Chain Reaction MH - Repressor Proteins MH - Sequence Analysis, DNA MH - Sequence Homology, Amino Acid PMC - PMC310662 EDAT- 1997/06/01 00:00 MHDA- 1997/06/01 00:01 PMCR- 1997/12/01 CRDT- 1997/06/01 00:00 PHST- 1997/06/01 00:00 [pubmed] PHST- 1997/06/01 00:01 [medline] PHST- 1997/06/01 00:00 [entrez] PHST- 1997/12/01 00:00 [pmc-release] AID - 10.1101/gr.7.6.615 [doi] PST - ppublish SO - Genome Res. 1997 Jun;7(6):615-24. doi: 10.1101/gr.7.6.615.