The human desmin locus: gene organization and LCR-mediated transcriptional control.
Locus control regions (LCRs) are defined by their ability to confer reproducible physiological levels of transgene expression in mice and therefore thought to possess the ability to generate dominantly a transcriptionally active chromatin structure. We report the first characterization of a muscle-cell-specific LCR, which is linked to the human desmin gene (DES). The DES LCR consists of five regions of muscle-specific DNase I hypersensitivity (HS) localized between -9 and -18 kb 5' of DES and reproducibly drives full physiological levels of expression in all muscle cell types. The DES LCR DNase I HS regions are highly conserved between humans and other mammals and can potentially bind a broad range of muscle-specific and ubiquitous transcription factors. Bioinformatics and direct molecular analysis show that the DES locus consists of three muscle-specific (DES) or muscle preferentially expressed genes (APEG1 and SPEG, the human orthologue of murine striated-muscle-specific serine/threonine protein kinase, Speg). The DES LCR may therefore regulate expression of SPEG and APEG1 as well as DES.
Nuclear Biology Group, Department of Medical and Molecular Genetics, King's College London School of Medicine, King's College London-Guy's Campus, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK.
Jennifer L Y
JL
Tam
Kostas
K
Triantaphyllopoulos
Helen
H
Todd
Selina
S
Raguz
Ton
T
de Wit
Jennifer E
JE
Morgan
Terence A
TA
Partridge
Eleni
E
Makrinou
Frank
F
Grosveld
Michael
M
Antoniou
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I; D003893:Desmin / Q000235:genetics*; D015870:Gene Expression; D008040:Genetic Linkage; D006801:Humans; D019901:Locus Control Region; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics; D009132:Muscles / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014158:Transcription, Genetic
D003893:Desmin; D009124:Muscle Proteins; D004247:DNA; D017346:Protein Serine-Threonine Kinases; C100675:SPEG protein, human; D003850:Deoxyribonuclease I