Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator

Wei, Y., Gokhale, R. H., Sonnenschein, A., Montgomery, K. M., Ingersoll, A., Arnosti, D. N. (October 2016) Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator. Development, 143 (19). pp. 3591-3603. ISSN 0950-1991

URL: https://www.ncbi.nlm.nih.gov/pubmed/27702787
DOI: 10.1242/dev.138073

Abstract

Insulin signaling plays key roles in development, growth and metabolism through dynamic control of glucose uptake, global protein translation and transcriptional regulation. Altered levels of insulin signaling are known to play key roles in development and disease, yet the molecular basis of such differential signaling remains obscure. Expression of the insulin receptor (InR) gene itself appears to play an important role, but the nature of the molecular wiring controlling InR transcription has not been elucidated. We characterized the regulatory elements driving Drosophila InR expression and found that the generally broad expression of this gene is belied by complex individual switch elements, the dynamic regulation of which reflects direct and indirect contributions of FOXO, EcR, Rbf and additional transcription factors through redundant elements dispersed throughout approximately 40 kb of non-coding regions. The control of InR transcription in response to nutritional and tissue-specific inputs represents an integration of multiple cis-regulatory elements, the structure and function of which may have been sculpted by evolutionary selection to provide a highly tailored set of signaling responses on developmental and tissue-specific levels.

Item Type: Paper
Uncontrolled Keywords: Ecdysone Insulin receptor Retinoblastoma Transcriptional enhancer dFOXO
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > cis-regulatory elements
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > insulin receptor
CSHL Authors:
Communities: CSHL labs > Vakoc lab
Depositing User: Matt Covey
Date: 1 October 2016
Date Deposited: 17 Mar 2017 21:29
Last Modified: 17 Mar 2017 21:29
PMCID: PMC5087611
Related URLs:
URI: http://repository.cshl.edu/id/eprint/34269

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