Title | Large-scale comparative sequence analysis of the human and murine Bruton's tyrosine kinase loci reveals conserved regulatory domains. |
Publication Type | Journal Article |
Year of Publication | 1997 |
Authors | Oeltjen, JC, Malley, TM, Muzny, DM, Miller, W, Gibbs, RA, Belmont, JW |
Journal | Genome Res |
Volume | 7 |
Issue | 4 |
Pagination | 315-29 |
Date Published | 1997 Apr |
ISSN | 1088-9051 |
Keywords | Agammaglobulinaemia Tyrosine Kinase, alpha-Galactosidase, Animals, Base Sequence, Conserved Sequence, Enhancer Elements, Genetic, Genetic Variation, Humans, Mice, Models, Genetic, Molecular Sequence Data, Promoter Regions, Genetic, Protein-Tyrosine Kinases, Recombinant Proteins, Regulatory Sequences, Nucleic Acid, Repetitive Sequences, Nucleic Acid, Sequence Alignment, Sequence Analysis, DNA, Sequence Homology, Nucleic Acid, Transcription Factors, Transcription, Genetic, Transfection |
Abstract | Large-scale genomic DNA sequencing of orthologous and paralogous loci in different species should contribute to a basic understanding of the evolution of both the protein-coding regions and noncoding regulatory elements. We compared 93 kb of human sequence to 89 kb of mouse sequence in the Bruton's tyrosine kinase (BTK) region. In addition to showing the conservation of both position and orientation of the five functionally unrelated genes in the region (BTK, alpha-D-galactosidase A, L44L, FTP-3, and FCI-12), the comparison revealed conservation of clusters of noncoding sequence flanking the first exon of each gene. Furthermore, in the sequence comparison at the BTK locus, the conservation of clusters of noncoding sequence extends throughout the locus; the noncoding sequence is more highly conserved in the BTK locus in comparison to the flanking loci. This suggests a correlation with the complex developmental regulation of expression of btk. To determine whether a highly conserved 3.5-kb segment flanking the first exon of BTK contains transcriptional regulatory signals, we tested various portions of the segment for promoter and expression activity in several appropriate cell lines. The results demonstrate the contribution of the conserved region flanking the first exon to the cell lineage-specific expression pattern of btk. These data show the usefulness of large scale sequence comparisons to focus investigation on regions of noncoding sequence that play essential roles in complex gene regulation. |
DOI | 10.1101/gr.7.4.315 |
Alternate Journal | Genome Res |
PubMed ID | 9110171 |
Grant List | LM05110 / LM / NLM NIH HHS / United States R01 HG 01459 / HG / NHGRI NIH HHS / United States R01 HL51232 / HL / NHLBI NIH HHS / United States |
Large-scale comparative sequence analysis of the human and murine Bruton's tyrosine kinase loci reveals conserved regulatory domains.
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