Comparative Genomic Analysis of Transcription Regulation Elements Involved in Human Map Kinase G-protein Coupling Pathway

The identification of cis-elements (motifs) in the regulatory regions of higher eukaryotes is an important and challenging problem in computational biology. Eukaryotic transcriptional regulatory mechanisms pose several difficulties for promoter analysis: including a high variance in the motif locations, frequently large divergence from motif consensus patterns, and a large amount of repetitive elements (confusing to many motif finding procedures). One promising approach to this difficult problem involves cross-species comparison. In this work we analyzed the full-length regulatory regions of genes involved in the G-protein coupling MAP kinase pathway and compared the results with ribosomal genes using human, mouse and rat genomic data. We found 19 high likely transcription factors (TFs) candidates for MAPK and 12 TFs for the ribosomal dataset. In the case of the MAPK dataset, regulatory regions of genes functionally grouped as receptors and MAP-core genes were found mostly highly conserved across the three species.

[1]  T. Hunter,et al.  Signaling—2000 and Beyond , 2000, Cell.

[2]  K. Lindblad-Toh,et al.  Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals , 2005, Nature.

[3]  M. Karin,et al.  Mammalian MAP kinase signalling cascades , 2001, Nature.

[4]  V. Pirrotta,et al.  The mcp element from the Drosophila melanogaster bithorax complex mediates long-distance regulatory interactions. , 1999, Genetics.

[5]  R. Sandberg,et al.  The molecular portrait of in vitro growth by meta-analysis of gene-expression profiles , 2005, Genome Biology.

[6]  Holger Karas,et al.  TRANSFAC: a database on transcription factors and their DNA binding sites , 1996, Nucleic Acids Res..

[7]  A. Brivanlou,et al.  Signal Transduction and the Control of Gene Expression , 2002, Science.

[8]  Kenta Nakai,et al.  MELINA: motif extraction from promoter regions of potentially co-regulated genes , 2003, Bioinform..

[9]  Dennis B. Troup,et al.  NCBI GEO: mining millions of expression profiles—database and tools , 2004, Nucleic Acids Res..

[10]  K. Nakai,et al.  Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. , 2004, Genome research.

[11]  Tatiana Tatusova,et al.  NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins , 2004, Nucleic Acids Res..

[12]  Kenta Nakai,et al.  DBTSS: DataBase of human Transcriptional Start Sites and full-length cDNAs , 2002, Nucleic Acids Res..

[13]  Tatiana A. Tatusova,et al.  NCBI Reference Sequence (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins , 2004, Nucleic Acids Res..

[14]  Kazunari Miyamichi,et al.  Negative Feedback Regulation Ensures the One Receptor-One Olfactory Neuron Rule in Mouse , 2003, Science.

[15]  Judith A. Blake,et al.  MGD: the Mouse Genome Database , 2003, Nucleic Acids Res..

[16]  Panayiotis V. Benos,et al.  FOOTER: a web tool for finding mammalian DNA regulatory regions using phylogenetic footprinting , 2005, Nucleic Acids Res..