A cis-regulatory logic simulator

Background  

A major goal of computational studies of gene regulation is to accurately predict the expression of genes based on the cis-regulatory content of their promoters. The development of computational methods to decode the interactions among cis-regulatory elements has been slow, in part, because it is difficult to know, without extensive experimental validation, whether a particular method identifies the correct cis-regulatory interactions that underlie a given set of expression data. There is an urgent need for test expression data in which the interactions among cis-regulatory sites that produce the data are known. The ability to rapidly generate such data sets would facilitate the development and comparison of computational methods that predict gene expression patterns from promoter sequence.     

Identification of tissue-specific cis-regulatory modules based on interactions between transcription factors

Background  

Evolutionary conservation has been used successfully to help identify cis-acting DNA regions that are important in regulating tissue-specific gene expression. Motivated by increasing evidence that some DNA regulatory regions are not evolutionary conserved, we have developed an approach for cis-regulatory region identification that does not rely upon evolutionary sequence conservation.     

Human promoter genomic composition demonstrates non-random groupings that reflect general cellular function

Background  

The purpose of this study is to determine whether or not there exists nonrandom grouping of cis-regulatory elements within gene promoters that can be perceived independent of gene expression data and whether or not there is any correlation between this grouping and the biological function of the gene.     

A method of predicting changes in human gene splicing induced by genetic variants in context of cis-acting elements

Background  

Polymorphic variants and mutations disrupting canonical splicing isoforms are among the leading causes of human hereditary disorders. While there is a substantial evidence of aberrant splicing causing Mendelian diseases, the implication of such events in multi-genic disorders is yet to be well understood. We have developed a new tool (SpliceScan II) for predicting the effects of genetic variants on splicing and cis-regulatory elements. The novel Bayesian non-canonical 5'GC splice site (SS) sensor used in our tool allows inference on non-canonical exons.     

<Emphasis Type="Italic">LTRharvest</Emphasis>, an efficient and flexible software for <Emphasis Type="Italic">de novo</Emphasis> detection of LTR retrotransposons

Background  

Transposable elements are abundant in eukaryotic genomes and it is believed that they have a significant impact on the evolution of gene and chromosome structure. While there are several completed eukaryotic genome projects, there are only few high quality genome wide annotations of transposable elements. Therefore, there is a considerable demand for computational identification of transposable elements. LTR retrotransposons, an important subclass of transposable elements, are well suited for computational identification, as they contain long terminal repeats (LTRs).     

Cross-species comparison significantly improves genome-wide prediction of cis-regulatory modules in Drosophila

Background  

The discovery of cis-regulatory modules in metazoan genomes is crucial for understanding the connection between genes and organism diversity. It is important to quantify how comparative genomics can improve computational detection of such modules.     

Some statistical properties of regulatory DNA sequences,and their use in predicting regulatory regions in the <Emphasis Type="Italic">Drosophila</Emphasis> genome: the fluffy-tail test

Background  

This paper addresses the problem of recognising DNA cis-regulatory modules which are located far from genes. Experimental procedures for this are slow and costly, and computational methods are hard, because they lack positional information.     

Cis-motifs upstream of the transcription and translation initiation sites are effectively revealed by their positional disequilibrium in eukaryote genomes using frequency distribution curves

Background  

The discovery of cis-regulatory motifs still remains a challenging task even though the number of sequenced genomes is constantly growing. Computational analyses using pattern search algorithms have been valuable in phylogenetic footprinting approaches as have expression profile experiments to predict co-occurring motifs. Surprisingly little is known about the nature of cis-regulatory element (CRE) distribution in promoters.     

Statistical power of phylo-HMM for evolutionarily conserved element detection

Background  

An important goal of comparative genomics is the identification of functional elements through conservation analysis. Phylo-HMM was recently introduced to detect conserved elements based on multiple genome alignments, but the method has not been rigorously evaluated.     

Evolutionary dynamics of a conserved sequence motif in the ribosomal genes of the ciliate <Emphasis Type="Italic">Paramecium</Emphasis>

Background  

In protozoa, the identification of preserved motifs by comparative genomics is often impeded by difficulties to generate reliable alignments for non-coding sequences. Moreover, the evolutionary dynamics of regulatory elements in 3' untranslated regions (both in protozoa and metazoa) remains a virtually unexplored issue.     

Cis-regulatory sequences in plants: Their importance,discovery, and future challenges

The identification and characterization of cis-regulatory DNA sequences and how they function to coordinate responses to developmental and environmental cues is of paramount importance to plant biology. Key to these regulatory processes are cis-regulatory modules (CRMs), which include enhancers and silencers. Despite the extraordinary advances in high-quality sequence assemblies and genome annotations, the identification and understanding of CRMs, and how they regulate gene expression, lag significantly behind. This is especially true for their distinguishing characteristics and activity states. Here, we review the current knowledge on CRMs and breakthrough technologies enabling identification, characterization, and validation of CRMs; we compare the genomic distributions of CRMs with respect to their target genes between different plant species, and discuss the role of transposable elements harboring CRMs in the evolution of gene expression. This is an exciting time to study cis-regulomes in plants; however, significant existing challenges need to be overcome to fully understand and appreciate the role of CRMs in plant biology and in crop improvement.

This review discusses the features of cis-regulatory sequences in plants, technologies enabling their identification, characterization, and validation, their organization into functional cis-regulatory modules, their genomic distributions with respect to target genes, and the role of transposable elements in their evolution.