Question: How are CRM (cis-regulatory modules) defined?

Context:
Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules.
In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules
This conserved sequence has therefore been proposed to act as a long-range, cis-acting regulator of limb-specific Shh expression. 
The conserved upstream sequence can activate gene expression from basal promoters in the brain vesicle, although it requires additional cis-regulatory sequences to fully activate the CNS-specific gene expression.
The genomic instructions used to regulate development are encoded within a set of functional DNA elements called cis-regulatory modules 
Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). 
However, studies on the cis-regulatory sequences mediating the synergistic effects of these transcription factors are complicated by the limited knowledge of notochord genes and cis-regulatory modules (CRMs) that are directly targeted by both.
The identification of transcription factor binding sites (TFBSs) and cis-regulatory modules (CRMs) is a crucial step in studying gene expression, but the computational method attempting to distinguish CRMs from NCNRs still remains a challenging problem due to the limited knowledge of specific interactions involved.
In eukaryotes, transcriptional regulation is usually mediated by interactions of multiple transcription factors (TFs) with their respective specific cis-regulatory elements (CREs) in the so-called cis-regulatory modules (CRMs) in DNA.
The transcriptional regulation of a metazoan gene depends on the cooperative action of multiple transcription factors that bind to cis-regulatory modules (CRMs) located in the neighborhood of the gene.
Dynamic in vivo binding of transcription factors to cis-regulatory modules of cer and gsc in the stepwise formation of the Spemann-Mangold organizer.
We also identified potential cis-regulatory modules (CRMs) defined as clusters of conserved TFBSs in the entire mouse genome.

Answer: Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules.
In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs).
Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs).  
CisMiner can be queried for the results presented in this work and can also perform a customized cis-regulatory module prediction on a query set of transcription factor binding sites provided by the user. In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules. Our web server is available at http://creme.dcode.org.