Cis-regulatory module

Cis-regulatory module (CRM) is a stretch of DNA, usually 100-1000 DNA base pairs in length, where a number of transcription factors can bind and regulate expression of nearby genes and regulate their transcription rates. They are labeled as cis because they are typically located on the same DNA strand as the genes they control as opposed to trans, which refers to effects on genes not located on the same strand or farther away, such as transcription factors. One cis-regulatory element can regulate several genes, and conversely, one gene can have several cis-regulatory modules.Cis-regulatory modules carry out their function by integrating the active transcription factors and the associated co-factors at a specific time and place in the cell where this information is read and an output is given.

Cis-regulatory modules are one of several types of functional regulatory elements. Regulatory elements are binding sites for transcription factors, which are involved in gene regulation.Cis-regulatory modules perform a large amount of developmental information processing.Cis-regulatory modules are non-random clusters at their specified target site that contain transcription factor binding sites.

The original definition presented cis-regulatory modules as enhancers of cis-acting DNA, which increased the rate of transcription from a linked promoter. However, this definition has changed to define cis-regulatory modules as a DNA sequence with transcription factor binding sites which are clustered into modular structures, including -but not limited to- locus control regions, promoters, enhancers, silencers, boundary control elements and other modulators.

Cis-regulatory modules can be divided into three classes; enhancers, which regulate gene expression positively;insulators, which work indirectly by interacting with other nearby cis-regulatory modules; and silencers that turn off expression of genes.

The design of cis-regulatory modules is such that transcription factors and epigenetic modifications serve as inputs, and the output of the module is the command given to the transcription machinery, which in turn determines the rate of gene transcription or whether it is turned on or off. There are two types of transcription factor inputs: those that determine when the target gene is to be expressed and those that serve as functional drivers, which come into play only during specific situations during development. These inputs can come from different time points, can represent different signal ligands, or can come from different domains or lineages of cells. However, a lot still remains unknown.

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