Trans-regulatory elements (TRE) are DNA sequences encoding upstream regulators (ie. trans-acting factors), which may modify or regulate the expression of distant genes.

Trans-acting In the field of molecular biology, ''trans''-acting (''trans''-regulatory, ''trans''-regulation), in general, means "acting from a different molecule" (''i.e.'', intermolecular). It may be considered the opposite of ''cis''-acting (''cis''-regula ...

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.

Trans vs cis elements

Trans-regulatory elements work through an

intermolecular An intermolecular force (IMF) (or secondary force) is the force that mediates interaction between molecules, including the electromagnetic forces of attraction or repulsion which act between atoms and other types of neighbouring particles, e.g. a ...

interaction between two different molecules and so are said to be " acting in trans". For example (1) a transcribed and

translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

protein derived from the trans-regulatory element; and a (2) DNA regulatory element that is adjacent to the regulated gene. 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, 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. Hence, they have higher resistance to genetic divergence, yet retains its susceptibility to mutations in upstream regulators. This accentuates the significance of genetic divergence within species due to cis- and trans-regulatory variants. 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. Other evolutionary models, such as the independent evolution of trans- or cis-regulatory elements, were deemed incompatible in regulatory systems. Co-evolution of the two regulatory elements was suggested to arise from the same lineage. 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. Following a TRE mutation, accumulation of CRE mutations act to fine-tune the mutative effect.

Examples

Trans-acting factors can be categorized by their interactions with the regulated genes, cis-acting elements of the genes, or the gene products.

DNA binding

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. Specific examples include: *

Transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

DNA editing

DNA editing proteins edit and permanently change gene sequence, and subsequently the gene expression of the cell. All progenies of the cell will inherit the edited gene sequence. DNA editing proteins often take part in the immune response system of both prokaryotes and eukaryotes, providing high variance in gene expression in adaptation to various pathogens. Specific examples include: *

RAG1 Recombination activating gene 1 also known as RAG-1 is a protein that in humans is encoded by the ''RAG1'' gene. The RAG1 and RAG2 genes are largely conserved in humans. 55.99% and 55.98% of the encoded amino acids contain no reported variants, r ...

/ RAG2 * TdT * Cas1/ Cas2

mRNA processing

mRNA processing acts as a form of post-transcriptional regulation, which mostly happens in eukaryotes. 3′ cleavage/polyadenylation and 5’ capping increase overall RNA stability, and the presence of 5’ cap allows ribosome binding for translation. RNA splicing allows the expression of various protein variants from the same gene. Specific examples include: * SR proteins *

Ribonucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating inte ...

** hnRNP **

snRNP snRNPs (pronounced "snurps"), or small nuclear ribonucleoproteins, are RNA-protein complexes that combine with unmodified pre-mRNA and various other proteins to form a spliceosome, a large RNA-protein molecular complex upon which splicing of pr ...

mRNA binding

mRNA binding allows repression of protein translation through direct blocking, degradation or cleavage of mRNA. Certain mRNA binding mechanisms have high specificity, which can act as a form of the intrinsic immune response during certain viral infections. Certain segmented RNA viruses can also regulate viral gene expression through RNA binding of another genome segment, however, the details of this mechanism are still unclear. Specific examples include: *

RNA binding protein RNA-binding proteins (often abbreviated as RBPs) are proteins that bind to the double or single stranded RNA in cells and participate in forming ribonucleoprotein complexes. RBPs contain various structural motifs, such as RNA recognition motif ...

siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating ...

miRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miR ...

piRNA Pirna (; hsb, Pěrno; ) is a town in Saxony, Germany and capital of the administrative district Sächsische Schweiz-Osterzgebirge. The town's population is over 37,000. Pirna is located near Dresden and is an important district town as well as ...

References

Gene expression {{Genetics-stub