Search for TF-encoding genes

Search for human-mouse and human-fugu CNEs associated with a TF-encoding gene

Search your DNA sequence in CNEs

View CNEs in GBrowse

Fugu Genome Project, IMCB

Transcription factors (TFs) are proteins that typically bind to DNA sequences (known as transcription factor binding sites) and lead to the activation or repression of target genes. TFs include sequence-specific activators and repressors, general transcription factors, co-factors and chromatin modifiers. The TFs that activate or repress target genes occupy crucial nodes in the gene regulatory networks (GRNs) of development and other biological processes, and thus the correct spatio-temporal expression of TF-encoding genes is vital for the correct expression of not only their immediate target genes but also other downstream genes. Hence, it is important to understand how TF-encoding genes themselves are regulated. The first important step in understanding the regulation of TF-encoding genes is the identification of cis-regulatory elements associated with them.

Comparative genomics is a powerful approach for identifying putative cis-regulatory elements. Due to the selective constraint on functional elements such as regulatory regions, cis-regulatory elements evolve slowly and therefore can be identified as conserved noncoding elements (CNEs) in sequence comparisons of related genomes. Vertebrates distantly related to humans are particularly useful in such comparisons since the signal-to-noise ratio in such comparisons is higher and most of the CNEs identified are likely to be functional elements. We have been using comparisons of human, mouse and fugu genes to identify putative cis-regulatory elements in the human genome. Since mammals and fugu diverged from their common ancestors about 420 Myr ago, fugu provides the highest stringency for identifying putative cis-regulatory elements in the human genome.

This database, called TFCONES (Transcription Factor genes & associated COnserved Noncoding ElementS), houses all human transcription factors and their homologs in mouse and fugu, and the details of CNEs identified in the orthologous set of TF-encoding genes in human, mouse and fugu. Orthologous TF loci (including the entire 5' and 3' flanking regions) in the three genomes were aligned using MLAGAN, a multiple alignment program that constructs a global alignment of long genomic sequences, and CNEs were predicted using VISTA, a visualization package for sequence comparisons. Individual TF-encoding genes and their associated CNEs may be retrieved from this database. These CNEs constitute a set of highly prioritized putative regulatory elements of TF-encoding genes that can be tested in in vitro and in vivo systems. Functional assay of these CNEs should help in understanding the molecular basis underlying the complex regulatory mechanisms of TF-encoding genes.

More details of this database can be found in the Methods page and in our publication:

Lee, A.P., Yang, Y., Brenner, S. and Venkatesh, B. (2007) TFCONES: A database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements. BMC Genomics, 8:441.

The Generic Genome Browser (GBrowse) is the work of scientists at Cold Spring Harbor Laboratory and University of California, Berkeley.

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