Mammalian comparative sequence analysis of the Agrp locus.
Agouti-related protein encodes a neuropeptide that stimulates food intake. Agrp expression in the brain is restricted to neurons in the arcuate nucleus of the hypothalamus and is elevated by states of negative energy balance. The molecular mechanisms underlying Agrp regulation, however, remain poorly defined. Using a combination of transgenic and comparative sequence analysis, we have previously identified a 760 bp conserved region upstream of Agrp which contains STAT binding elements that participate in Agrp transcriptional regulation. In this study, we attempt to improve the specificity for detecting conserved elements in this region by comparing genomic sequences from 10 mammalian species. Our analysis reveals a symmetrical organization of conserved sequences upstream of Agrp, which cluster into two inverted repeat elements. Conserved sequences within these elements suggest a role for homeodomain proteins in the regulation of Agrp and provide additional targets for functional evaluation.
Department of Genetics, Stanford University, Stanford, California, United States of America.
Christopher B
CB
Kaelin
Gregory M
GM
Cooper
Arend
A
Sidow
Gregory S
GS
Barsh
D054369:Agouti-Related Protein / Q000235:genetics*; D000818:Animals; D030801:Animals, Genetically Modified; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D055029:Inverted Repeat Sequences; D008322:Mammals / Q000235:genetics*; D008969:Molecular Sequence Data; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D054369:Agouti-Related Protein; D050796:STAT3 Transcription Factor