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

R. Chrast, H. S. Scott, H. Chen, Jun Kudo, C. Rossier, S. Minoshma, Y. Wang, N. Shimizu, S. E. Antonarakis

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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 ~ 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.

Original languageEnglish
Pages (from-to)615-624
Number of pages10
JournalGenome Research
Volume7
Issue number6
Publication statusPublished - 1997
Externally publishedYes

Fingerprint

Down Syndrome
Drosophila
Organism Cloning
Chromosomes
Genes
Neurogenesis
Exons
Transcription Factors
Clone Cells
Chromosomes, Human, Pair 21
Messenger RNA
Human Chromosomes
Dimerization
Diptera
Northern Blotting
Fruit
Protein Isoforms
Phenotype
Kidney

ASJC Scopus subject areas

  • Genetics

Cite this

Chrast, R., Scott, H. S., Chen, H., Kudo, J., Rossier, C., Minoshma, S., ... Antonarakis, S. E. (1997). 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. Genome Research, 7(6), 615-624.

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. / Chrast, R.; Scott, H. S.; Chen, H.; Kudo, Jun; Rossier, C.; Minoshma, S.; Wang, Y.; Shimizu, N.; Antonarakis, S. E.

In: Genome Research, Vol. 7, No. 6, 1997, p. 615-624.

Research output: Contribution to journalArticle

Chrast, R, Scott, HS, Chen, H, Kudo, J, Rossier, C, Minoshma, S, Wang, Y, Shimizu, N & Antonarakis, SE 1997, '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', Genome Research, vol. 7, no. 6, pp. 615-624.
Chrast, R. ; Scott, H. S. ; Chen, H. ; Kudo, Jun ; Rossier, C. ; Minoshma, S. ; Wang, Y. ; Shimizu, N. ; Antonarakis, S. E. / 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. In: Genome Research. 1997 ; Vol. 7, No. 6. pp. 615-624.
@article{843543df659245d8ad3f99d3f1f061f7,
title = "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",
abstract = "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 ~ 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.",
author = "R. Chrast and Scott, {H. S.} and H. Chen and Jun Kudo and C. Rossier and S. Minoshma and Y. Wang and N. Shimizu and Antonarakis, {S. E.}",
year = "1997",
language = "English",
volume = "7",
pages = "615--624",
journal = "Genome Research",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "6",

}

TY - JOUR

T1 - 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

AU - Chrast, R.

AU - Scott, H. S.

AU - Chen, H.

AU - Kudo, Jun

AU - Rossier, C.

AU - Minoshma, S.

AU - Wang, Y.

AU - Shimizu, N.

AU - Antonarakis, S. E.

PY - 1997

Y1 - 1997

N2 - 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 ~ 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.

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 ~ 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.

UR - http://www.scopus.com/inward/record.url?scp=0030810722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030810722&partnerID=8YFLogxK

M3 - Article

C2 - 9199934

AN - SCOPUS:0030810722

VL - 7

SP - 615

EP - 624

JO - Genome Research

JF - Genome Research

SN - 1088-9051

IS - 6

ER -