Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals.
Comprehensive identification of all functional elements encoded in the human genome is a fundamental need in biomedical research. Here, we present a comparative analysis of the human, mouse, rat and dog genomes to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs). The promoter analysis yields 174 candidate motifs, including most previously known transcription-factor binding sites and 105 new motifs. The 3'-UTR analysis yields 106 motifs likely to be involved in post-transcriptional regulation. Nearly one-half are associated with microRNAs (miRNAs), leading to the discovery of many new miRNA genes and their likely target genes. Our results suggest that previous estimates of the number of human miRNA genes were low, and that miRNAs regulate at least 20% of human genes. The overall results provide a systematic view of gene regulation in the human, which will be refined as additional mammalian genomes become available.
Xie
Xiaohui
X
Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA.
Lu
Jun
J
Kulbokas
E J
EJ
Golub
Todd R
TR
Mootha
Vamsi
V
Lindblad-Toh
Kerstin
K
Lander
Eric S
ES
Kellis
Manolis
M
D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D004285:Dogs; D020869:Gene Expression Profiling; D006801:Humans; D008322:Mammals / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D016415:Sequence Alignment
D020413:3' Untranslated Regions; D035683:MicroRNAs
Mol Cell Biol. 1992 Nov;12(11):4919-29
1406669
IUBMB Life. 2003 Jul;55(7):359-66
14584586
Nature. 2004 Apr 1;428(6982):493-521
15057822
Genome Res. 2003 Jan;13(1):103-7
12529312
Cell. 2005 Jan 14;120(1):21-4
15652478
Nat Genet. 2000 Oct;26(2):225-8
11017083
Cell. 2005 Jan 14;120(1):15-20
15652477
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D109-11
14681370
Nature. 2005 Feb 17;433(7027):769-73
15685193
Cell. 2003 Dec 26;115(7):787-98
14697198
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1993 Mar;47(3):2083-2099
9960229
Science. 2003 Feb 28;299(5611):1391-4
12610304
Mol Endocrinol. 1997 Mar;11(3):342-52
9058380
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W249-52
15215389
Genome Res. 2004 May;14(5):852-9
15078857
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7
15075390
Nat Rev Genet. 2003 Aug;4(8):626-37
12897774
Nat Genet. 2002 Apr;30(4):363-4
11896390
Nucleic Acids Res. 2003 Jul 1;31(13):3429-31
12824340
Cell. 2004 Jan 23;116(2):281-97
14744438
Science. 2003 Jul 4;301(5629):71-6
12775844
Nature. 2002 Dec 5;420(6915):520-62
12466850
Genome Res. 2000 Sep;10(9):1304-6
10984448
Genome Res. 2004 Apr;14(4):708-15
15060014
Nucleic Acids Res. 2000 Jan 1;28(1):126-8
10592200
RNA. 2003 Mar;9(3):277-9
12592000
Trends Biochem Sci. 1995 Nov;20(11):465-70
8578590
Nature. 2003 May 15;423(6937):241-54
12748633
BMC Bioinformatics. 2004 Oct 28;5:170
15511292
Nucleic Acids Res. 2003 Jan 1;31(1):374-8
12520026
Science. 2001 Oct 5;294(5540):169-73
11588264
Science. 2003 Mar 7;299(5612):1540
12624257
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6570-5
15100410
PLoS Biol. 2005 Jan;3(1):e10
15660152
Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4795-800
15778292
Science. 2004 May 28;304(5675):1321-5
15131266
Nature. 2001 Feb 15;409(6822):860-921
11237011