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Type: Journal article
Title: Comparative and functional analyses of LYL1 loci establish marsupial sequences as a model for phylogenetic footprinting
Author: Chapman, M.
Charchar, F.
Kinston, S.
Bird, C.
Grafham, D.
Rogers, J.
Grutzner, F.
Graves, J.
Green, A.
Gottgens, B.
Citation: Genomics, 2003; 81(3):249-259
Publisher: Academic Press Inc Elsevier Science
Issue Date: 2003
ISSN: 0888-7543
Statement of
Michael A. Chapman, Fadi J. Charchar, Sarah Kinston, Christine P. Bird, Darren Grafham, Jane Rogers, Frank Grützner, Jennifer A. Marshall Graves, Anthony R. Green and Berthold Göttgens
Abstract: Comparative genomic sequence analysis is a powerful technique for identifying regulatory regions in genomic DNA. However, its utility largely depends on the evolutionary distances between the species involved. Here we describe the screening of a genomic BAC library from the stripe-faced dunnart, Sminthopsis macroura, formerly known as the narrow-footed marsupial mouse. We isolated a clone containing the LYL1 locus, completely sequenced the 60.6-kb insert, and compared it with orthologous human and mouse sequences. Noncoding homology was substantially reduced in the human/dunnart analysis compared with human/mouse, yet we could readily identify all promoters and exons. Human/mouse/dunnart alignments of the LYL1 candidate promoter allowed us to identify putative transcription factor binding sites, revealing a pattern highly reminiscent of critical regulatory regions of the LYL1 paralogue, SCL. This newly identified LYL1 promoter showed strong activity in myeloid progenitor cells and was bound in vivo by Fli1, Elf1, and Gata2-transcription factors all previously shown to bind to the SCL stem cell enhancer. This study represents the first large-scale comparative analysis involving marsupial genomic sequence and demonstrates that such comparisons provide a powerful approach to characterizing mammalian regulatory elements.
Keywords: Animals; Marsupialia; DNA-Binding Proteins; Neoplasm Proteins; DNA; Chromosome Mapping; Phylogeny; Amino Acid Sequence; Base Sequence; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Models, Genetic; Molecular Sequence Data; Basic Helix-Loop-Helix Transcription Factors; Promoter Regions, Genetic
Description: Copyright © 2003 Elsevier Science
RMID: 0020064687
DOI: 10.1016/S0888-7543(03)00005-3
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Appears in Collections:Molecular and Biomedical Science publications
Environment Institute Leaders publications

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