Abstract
Regulation of gene expression influences almost all biological processes in an organism; sequence-specific DNA-binding transcription factors are critical to this control. For most genomes, the repertoire of transcription factors is only partially known. Hitherto transcription factor identification has been largely based on genome annotation pipelines that use pairwise sequence comparisons, which detect only those factors similar to known genes, or on functional classification schemes that amalgamate many types of proteins into the category of 'transcription factor'. Using a novel transcription factor identification method, the DBD transcription factor database fills this void, providing genome-wide transcription factor predictions for organisms from across the tree of life. The prediction method behind DBD identifies sequence-specific DNA-binding transcription factors through homology using profile hidden Markov models (HMMs) of domains. Thus, it is limited to factors that are homologus to those HMMs. The collection of HMMs is taken from two existing databases (Pfam and SUPERFAMILY), and is limited to models that exclusively detect transcription factors that specifically recognize DNA sequences. It does not include basal transcription factors or chromatin-associated proteins, for instance. Based on comparison with experimentally verified annotation, the prediction procedure is between 95% and 99% accurate. Between one quarter and one-half of our genome-wide predicted transcription factors represent previously uncharacterized proteins. The DBD (www.transcriptionfactor.org) consists of predicted transcription factor repertoires for 150 completely sequenced genomes, their domain assignments and the hand curated list of DNA-binding domain HMMs. Users can browse, search or download the predictions by genome, domain family or sequence identifier, view families of transcription factors based on domain architecture and receive predictions for a protein sequence.
MeSH Terms
Animals
DNA-Binding Proteins/chemistry
Databases, Protein
Internet
Markov Chains
Mice
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Transcription Factors/chemistry
User-Computer Interface
Chemicals
DNA-Binding Proteins
Transcription Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kummerfeld Sarah K
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK. skk@mrc-lmb.cam.ac.uk
Teichmann Sarah A
References (27)
27 references, click to expand
-
The SUPERFAMILY database in 2004: additions and improvements.
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D235-9
PMID: 14681402
-
RegulonDB (version 4.0): transcriptional regulation, operon organization and growth conditions in Escherichia coli K-12.
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D303-6
PMID: 14681419
-
Evolution of protein superfamilies and bacterial genome size.
J Mol Biol. 2004 Feb 27;336(4):871-87
PMID: 15095866
-
Structure and evolution of transcriptional regulatory networks.
Curr Opin Struct Biol. 2004 Jun;14(3):283-91
PMID: 15193307
-
A genome-wide and nonredundant mouse transcription factor database.
Biochem Biophys Res Commun. 2004 Sep 24;322(3):787-93
PMID: 15336533
-
Transcriptional regulatory code of a eukaryotic genome.
Nature. 2004 Sep 2;431(7004):99-104
PMID: 15343339
-
Genomic analysis of regulatory network dynamics reveals large topological changes.
Nature. 2004 Sep 16;431(7006):308-12
PMID: 15372033
-
An ORFeome-based analysis of human transcription factor genes and the construction of a microarray to interrogate their expression.
Genome Res. 2004 Oct;14(10B):2041-7
PMID: 15489324
-
SCOP: a structural classification of proteins database for the investigation of sequences and structures.
J Mol Biol. 1995 Apr 7;247(4):536-40
PMID: 7723011
-
The Universal Protein Resource (UniProt).
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D154-9
PMID: 15608167
-
The Protein Data Bank.
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
PMID: 10592235
-
TRANSFAC: an integrated system for gene expression regulation.
Nucleic Acids Res. 2000 Jan 1;28(1):316-9
PMID: 10592259
-
Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
Nat Genet. 2000 May;25(1):25-9
PMID: 10802651
-
Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes.
Science. 2000 Dec 15;290(5499):2105-10
PMID: 11118137
-
Extensive domain shuffling in transcription regulators of DNA viruses and implications for the origin of fungal APSES transcription factors.
Genome Biol. 2002;3(3):RESEARCH0012
PMID: 11897024
-
Transcriptional regulatory networks in Saccharomyces cerevisiae.
Science. 2002 Oct 25;298(5594):799-804
PMID: 12399584
-
MGD: the Mouse Genome Database.
Nucleic Acids Res. 2003 Jan 1;31(1):193-5
PMID: 12519980
-
Evolution of transcription factors and the gene regulatory network in Escherichia coli.
Nucleic Acids Res. 2003 Feb 15;31(4):1234-44
PMID: 12582243
-
Systematic characterization of the zinc-finger-containing proteins in the mouse transcriptome.
Genome Res. 2003 Jun;13(6B):1430-42
PMID: 12819142
-
MATCH: A tool for searching transcription factor binding sites in DNA sequences.
Nucleic Acids Res. 2003 Jul 1;31(13):3576-9
PMID: 12824369
-
Scaling laws in the functional content of genomes.
Trends Genet. 2003 Sep;19(9):479-84
PMID: 12957540
-
DBTBS: database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics.
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D75-7
PMID: 14681362
-
JASPAR: an open-access database for eukaryotic transcription factor binding profiles.
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D91-4
PMID: 14681366
-
The Pfam protein families database.
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D138-41
PMID: 14681378
-
TrSDB: a proteome database of transcription factors.
Nucleic Acids Res. 2004 Jan 1;32(Database issue):D171-3
PMID: 14681387
-
FlyBase: genes and gene models.
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D390-5
PMID: 15608223
-
The MAPPER database: a multi-genome catalog of putative transcription factor binding sites.
Nucleic Acids Res. 2005 Jan 1;33(Database issue):D91-7
PMID: 15608292