Identification of a coordinate regulator of interleukins 4, 13 and 5 by cross-species sequence comparisons

Journal Article · Sun Dec 12 04:00:00 EST 1999 · Science

OSTI ID:767564

Loots, Gabriela G ^[1]; Locksley, Richard M; Blankespoor, Catherine M; Wang, Zhi-En; Miller, Webb; Rubin, Edward M; Frazer, Kelly A

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1. LBNL Library

Regulatory elements, such as locus control regions (LCRs), that act over large genomic intervals to influence the expression patterns of genes have been difficult to Regulatory elements, such as locus control regions (LCRs), that act over large genomic intervals to influence the expression patterns of genes have been difficult to Regulatory elements, such as locus control regions (LCRs), that act over large genomic intervals to influence the expression patterns of genes have been difficult to Regulatory elements, such as locus control regions (LCRs), that act over large genomic intervals to influence the expression patterns of genes have been difficult to identify using standard molecular biology approaches. In this study we exploited a comparative sequence-based strategy to find non-coding sequences with the physical properties of LCR elements in the human 5q31 interleukin gene cluster region. Comparative analysis of {approximately} 1 Mb of orthologous human (5q31) and mouse (chromosome 11) sequenc es identified 90 conserved non-coding elements (3 100 bp in length and 3 70% identity). Fifteen of the non-coding elements were experimentally characterized, of which 12 were determined to be single copy in the human genome and 10 to be present (3 75% identity) in at least 2 mammals in addition to humans and mice. The largest non-coding sequence identified (401 bp in length) was conserved both with regard to sequence ({approximately}80% identity in mice, humans, cows, dogs, rabbits) and genomic location (in the IL-4 - IL-13 intergenic region in the 4 mammals examined). Functional characterization of this element in YAC transgenic mice revealed it to be a potent regulator of IL-4, IL-13 and IL-5 expression - genes spread over 120 kb.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: National Institutes of Health (US)
• DOE Contract Number: AC03-76SF00098
• OSTI ID: 767564
• Report Number(s): LBNL--44794
• Journal Information: Science, Journal Name: Science Journal Issue: 5463 Vol. 288; ISSN 0193-4511; ISSN SCEHDK
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
COWS
FUNCTIONALS
GENES
INTERLEUKIN HUMAN MOUSE ASTHMA INFLAMMATORY DISEASES
LYMPHOKINES
MAMMALS
MICE
MOLECULAR BIOLOGY
PHYSICAL PROPERTIES
RABBITS
TRANSGENIC MICE