Introduction
Binding site discovery:
-Computational -Experimental
Cis-regulatory evolution
Organisms
-Yeast
-Fly
-Mouse
-Human
Binding site degeneracy
Functional variants
Cis-regulatory code
Regulatory networks

Computional binding site prediction
The process of identifying transcription –factor binding sites is challenging because of limited genome-wide experimental data identifying true binding sites, because not all potential binding sites are bound by a TF, because binding is not always specific, because not all bound sites may actually contribute to expression, and because binding sites act combinatorially and may not be constitutively active. In recent years various types of computational methods have been used to detect these sites.

Software and tools
Ahab is an algorithm which was designed to detect enhancers and binding sites for transcription factors in the genomes of multicellular organisms
TFSearch - Searching Transcription Factor Binding Sites
OTFBS - Over-represented Transcription Factor Binding Site Prediction Tool
PROMO - Prediction of Transcription Factor Binding Sites
AlignACE - Aligns Nucleic Acid Conserved Elements - finds sequence elements conserved in a set of DNA sequences.
ScanACE - Scans for Nucleic Acid Conserved Elements - using a weight matrix approach, and returns information about the genomic environment.
ANN-Spec - UNIX program for discovering motifs in biological sequences. by finding ungapped local multiple sequence alignments.
TFM-Explorer - Transcription Factor Matrix Explorer - is a program for analyzing regulatory regions of eukaryotic genomes
JCUBIC is a Java-based GUI for CUBIC program which can be used for transcription factor binding site prediction.
PROMOCO : protein binding site prediction; includes the graphical user interface, JPromoco.
Stubb - Search for clusters of cis-regulatory binding sites.

Integrated Prediction and Visualization Workbenches
SegVISTA- a viewer of sequences and their annotations; now with a Motif module for integrating transcriptional regulation analysis tools.
Sockeye has been developed with a focus on displaying potential gene regulatory regions and for running and visualizing the results from regulatory element detection approaches and algorithms.
TOUCAN is a workbench for regulatory sequence analysis on metazoan genomes
PlantCARE,a database of plant cis-acting regulatory elements and a portal to tools for in silico analysis of promoter sequences.
PAINT: Promoter Analysis and Interaction Network Toolset (V 3.5)
TESS - Transcription Element Search System
CREAD - Comprehensive Regulatory Element Analysis and Detection

Databases and Datasets
RegulonDB offers downloadable sets of data and predictions.
cis RED The cisRED database holds conserved sequence motifs identified by genome scale motif discovery, similarity, clustering, co-occurrence and coexpression calculations
TRANSPro systematic promoter analysis of co-regulated genes. Known transcription factor binding sites are indicated.

Primary Literature
2003
Prediction of regulatory networks: genome-wide identification of transcription factor targets from gene expression data Jiang Qian , Jimmy Lin , Nicholas M. Luscombe , Haiyuan Yu and Mark Gerstein. Bioinformatics

Computational prediction of transcription-factor binding site locations. Bulyk ML. Genome Biology

2002
Discovery of regulatory elements by a computational method for phylogenetic footprinting. Blanchette, M. and Tompa, M. Genome Research

2000
Computational identification of cis –regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae. JD Hughes, PW Estep, S Tavazoie and GM. ChurchJ. Mol.Biol

Operons in Escherichia coli: genomic analyses and predictions. Salgado H, Moreno-Hagelsieb G, Smith TF, Collado-Vides J. PNAS

1999
From fold predictions to function predictions: automation of functional site conservation analysis for functional genome predictions. Zhang B, Rychlewski L, Pawlowski K, Fetrow JS, Skolnick J, Godzik A. Protein Science

Models for prediction and recognition of eukaryotic promoters. Werner, T. Mammalian Genome.

1995
Predicting Pol II promoter sequences using transcription factor binding sites. Prestridge DS. J Mol Biol.

1993.
Computer-assisted prediction, classification, and delimitation of protein binding sites in nucleic acids. K Frech, G Herrmann, and T Werner. Nucleic Acids Res

Labs
Zhang Lab: mathematical and statistical methods to identify functional elements in eukaryotic genomes