The cis-regulatory elements act as binding sites for specific proteins known as the transcription factors which either inhibit or enhance the transcription process. The trans-regulatory elements, on the other hand, are composed of DNA sequences which encode transcription factors.
What is the difference between cis regulatory elements and trans regulatory elements?
Additionally, each trans-regulatory element affects a large number of genes on both alleles, while cis-regulatory element is allele specific and only controls genes nearby. Exonic and promoter sequences of the genes are significantly more conserved than the genes in cis- and trans- regulatory elements.
What is the difference between trans acting and cis acting elements?
Cis-acting elements - DNA sequences in the vicinity of the structural portion of a gene that are required for gene expression. ... Trans-acting factors - factors, usually considered to be proteins, that bind to the cis-acting sequences to control gene expression.
How do trans-acting factors interact with cis-regulatory elements?
Trans-acting factors interact with cis-regulatory elements to regulate gene expression. TRE mediates expression profiles of a large number of genes via trans-acting factors. While TRE mutations affect gene expression, it is also one of the main driving factors for evolutionary divergence in gene expression.
What is the difference between cis and cis-regulatory elements?
This is in contrast to cis-regulatory elements that work through an intramolecular interaction between different parts of the same molecule: (1) a gene; and (2) an adjacent regulatory element for that gene in the same DNA molecule.
What is a cis-regulatory module?
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.
Why are cis regulatory modules difficult to identify?
Problems in identification arise because often scientists find themselves with a small set of known transcription factors, so it makes it harder to identify statistically significant clusters of transcription factor binding sites. Additionally, high costs limit the use of large whole genome tiling arrays.
What is the function of CREs?
CREs function to control transcription by acting nearby or within a gene. The most well characterized types of CREs are enhancers and promoters. Both of these sequence elements are structural regions of DNA that serve as transcriptional regulators. Cis -regulatory modules are one of several types of functional regulatory elements.
How do enhancers affect transcription?
Multiple enhancers can act in a coordinated fashion to regulate transcription of one gene. A number of genome-wide sequencing projects have revealed that enhancers are often transcribed to long non-coding RNA (lncRNA) or enhancer RNA (eRNA), whose changes in levels frequently correlate with those of the target gene mRNA.
What is a CIS module?
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 ...
What does the prefix cis mean?
The Latin prefix cis means "on this side", i.e. on the same molecule of DNA as the gene (s) to be transcribed. CRMs are stretches 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.
Why are the architecture and the arrangement of the transcription factor binding sites critical?
The architecture and the arrangement of the transcription factor binding sites are critical because disruption of the arrangement could cancel out the function. Functional flexible cis -regulatory modules are called billboards. Their transcriptional output is the summation effect of the bound transcription factors.
What is a cis regulatory element?
This is in contrast to cis-regulatory elements that work through an intramolecular interaction between different parts of the same molecule: (1) a gene; and (2) an adjacent regulatory element for that gene in the same DNA molecule. Additionally, each trans-regulatory element affects a large number of genes on both alleles, ...
Why do trans and cis regulate?
Trans- and cis-regulatory elements co-evolved rapidly in large-scale to maintain gene expression. They often act in opposite directions, one up-regulates while another down-regulates, to compensate for their effects on the exonic and promoter gene they act on.
How does DNA binding trans-acting factor regulate gene expression?
DNA binding trans-acting factors regulate gene expression by interfering with the gene itself or cis-acting elements of the gene, which lead to changes in transcription activities. This can be direct initiation of transcription. promotion or repression of transcriptional protein activities.
What are the trans-acting factors in alternative splicing?
Alternative splicing is a key mechanism that is involved in gene expression regulation. In the alternative splicing, trans-acting factors such as SR protein, hnRNP and snRNP control this mechanism by acting in trans. SR protein promotes the spliceosome assembly by interacting with snRNP (e.g. U1, U2) and splicing factors (e.g. U2AF65), and it can also antagonize the activity of hnRNP that inhibits splicing.
How does TRE affect gene expression?
TRE mediates expression profiles of a large number of genes via trans-acting factors. While TRE mutations affect gene expression, it is also one of the main driving factors for evolutionary divergence in gene expression.
How do trans-regulatory elements work?
Trans-regulatory elements work through an intermolecular interaction between two different molecules and so are said to be " acting in trans ". For example (1) a transcribed and translated transcription factor protein derived from the trans-regulatory element; and a (2) DNA regulatory element that is adjacent to the regulated gene.
Why is TRE more evolutionary constraint than cis-regulatory element?
TRE is more evolutionary constraint than cis-regulatory element, suggesting a hypothesis that TRE mutations are corrected by CRE mutations to maintain stability in gene expression. This makes biological sense, due to TRE’s effect on a broad range of genes and CRE's compensatory effect on specific genes.
Summary
Examples
An example of a cis-acting regulatory sequence is the operator in the lac operon. This DNA sequence is bound by the lac repressor, which, in turn, prevents transcription of the adjacent genes on the same DNA molecule. The lac operator is, thus, considered to "act in cis" on the regulation of the nearby genes. The operator itself does not code for any protein or RNA.
In contrast, trans-regulatory elements are diffusible factors, usually proteins, that may modify th…
Overview
The genome of an organism contains anywhere from a few hundred to thousands of different genes, all encoding a singular product or more. For numerous reasons, including organizational maintenance, energy conservation, and generating phenotypic variance, it is important that genes are only expressed when they are needed. The most efficient way for an organism to regulate gen…
Classification
Cis-regulatory modules can be characterized by the information processing that they encode and the organization of their transcription factor binding sites. Additionally, cis-regulatory modules are also characterized by the way they affect the probability, proportion, and rate of transcription. Highly cooperative and coordinated cis-regulatory modules are classified as enhanceosomes. The architecture and the arrangement of the transcription factor binding sites are critical because di…
Evolutionary role
CREs have an important evolutionary role. The coding regions of genes are often well conserved among organisms; yet different organisms display marked phenotypic diversity. It has been found that polymorphisms occurring within non-coding sequences have a profound effect on phenotype by altering gene expression. Mutations arising within a CRE can generate expression variance by changing the way TFs bind. Tighter or looser binding of regulatory proteins will lead to up- or do…
Cis-regulatory module in gene regulatory network
The function of a gene regulatory network depends on the architecture of the nodes, whose function is dependent on the multiple cis-regulatory modules. The layout of cis-regulatory modules can provide enough information to generate spatial and temporal patterns of gene expression. During development each domain, where each domain represents a different spatial regions of the embryo, of gene expression will be under the control of different cis-regulatory m…
Mode of action
Cis-regulatory modules can regulate their target genes over large distances. Several models have been proposed to describe the way that these modules may communicate with their target gene promoter. These include the DNA scanning model, the DNA sequence looping model and the facilitated tracking model. In the DNA scanning model, the transcription factor and cofactor complex form at the cis-regulatory module and then continues to move along the DNA sequenc…
Identification and computational prediction
Besides experimentally determining CRMs, there are various bioinformatics algorithms for predicting them. Most algorithms try to search for significant combinations of transcription factor binding sites (DNA binding sites) in promoter sequences of co-expressed genes. More advanced methods combine the search for significant motifs with correlation in gene expression datasets between transcription factors and target genes. Both methods have been implemented, for exam…