cis-elements are DNA sequences that are located on the same strand of DNA as a gene, and they regulate the transcription of that gene. Cis-elements can be located upstream (5') or downstream (3') of the gene, or even within the gene itself.
Cis-regulatory elements, such as promoters, enhancers, and silencers, are regions of non-coding DNA, which regulate the transcription of nearby genes
- DNA-binding domain: A cis-element that is recognized by DNA-binding proteins, such as transcription factors and chromatin modifiers. Examples of DNA-binding domains include the zinc finger domain, the helix-turn-helix domain, and the leucine zipper domain.
- Epigenetic marks: Cis-elements that are not DNA sequences, but rather chemical modifications of DNA or histone proteins that can affect gene expression. For example, DNA methylation is a common epigenetic mark that can silence gene expression by recruiting repressive trans-factors.
- Enhancer: A cis-element that can be located far away from the gene it regulates, and that can increase transcription by binding to specific trans-factors.
- Insulator: A cis-element that can prevent the spread of chromatin modifications and regulate the interactions between cis-elements and trans-factors. Insulators can be located between genes or within genes, and they play a role in maintaining the integrity of chromatin domains.
- Promoter: A common cis-element located upstream of a gene that is recognized by RNA polymerase and other transcription factors to initiate transcription.
- Poly(A) signal: A cis-element that is recognized by the polyadenylation machinery to add a poly(A) tail to the 3' end of an mRNA molecule.
- Silencer: A cis-element that can be located upstream or downstream of a gene, and that can decrease transcription by binding to specific trans-factors.
- Polyadenylation signal: A cis-element located downstream of a gene that signals the addition of a poly(A) tail to the 3' end of the mRNA.
- Response element: A cis-element that is recognized by a specific trans-factor, such as a transcription factor or hormone receptor, to activate or repress transcription in response to a particular signal or stimulus.
- RNA polymerase II C-terminal domain: A cis-element that is located at the carboxy-terminal end of the RNA polymerase II subunit and is involved in the regulation of transcriptional elongation and termination.
- Polycomb response element: A cis-element that is recognized by polycomb group proteins to establish and maintain gene silencing during development and differentiation.
- RNA-binding protein motif: A cis-element that is recognized by RNA-binding proteins to regulate RNA processing, stability, and translation. Examples of RNA-binding protein motifs include the AU-rich element (ARE) and the GU-rich element (GRE).
Trans-factors are molecules that bind to cis-elements and regulate gene expression. These molecules can include transcription factors, RNA-binding proteins, and other regulatory proteins. Trans-factors can bind to cis-elements located near the gene, or they can bind to cis-elements located far away on the same chromosome, or even on a different chromosome.
trans-regulatory factors regulate (or modify) the expression of distant genes by combining with their target sequences
- Alternative splicing factor: A trans-factor that can regulate alternative splicing of pre-mRNA, which is the process of generating multiple mRNA isoforms from a single gene. Examples of alternative splicing factors include the serine/arginine-rich (SR) proteins and the heterogeneous nuclear ribonucleoproteins (hnRNPs).
- Chromatin remodeling complex: A trans-factor that can alter the structure of chromatin to regulate gene expression. Chromatin remodeling complexes can move, eject, or reposition nucleosomes to expose or hide cis-elements from trans-factors.
- Chromatin modifier: A trans-factor that can modify chromatin structure by adding or removing chemical marks from histone proteins. Examples of chromatin modifiers include the histone methyltransferases and histone deacetylases.
- Chromatin remodeler: A trans-factor that can alter the structure of chromatin by sliding, ejecting, or repositioning nucleosomes. Examples of chromatin remodelers include the SWI/SNF complex and the ISWI complex.
- Chromatin insulator binding protein: A trans-factor that binds to chromatin insulators and regulates the interactions between cis-elements and trans-factors. Examples of chromatin insulator binding proteins include the CCCTC-binding factor (CTCF) and the boundary element-associated factor (BEAF).
- DNA methyltransferase: A trans-factor that can add a methyl group to cytosine residues in DNA, leading to gene silencing. DNA methyltransferases are involved in the process of DNA methylation, which is an epigenetic mechanism of gene regulation.
- Histone acetyltransferase: A trans-factor that can modify histone proteins by adding acetyl groups to lysine residues, leading to a more open chromatin structure and increased transcription. Examples of histone acetyltransferases include the p300/CBP family of proteins.
- MicroRNA: A trans-factor that binds to specific RNA sequences to regulate mRNA stability and translation. MicroRNAs are small non-coding RNAs that can base-pair with target mRNAs and inhibit their translation.
- Nuclear receptors: A class of transcription factors that bind to specific cis-elements in DNA in response to hormones, vitamins, and other signaling molecules. Nuclear receptors include the estrogen receptor, the androgen receptor, and the vitamin D receptor.
- Polycomb group proteins: A group of trans-factors that can repress gene expression by modifying chromatin structure. Polycomb group proteins can bind to specific cis-elements and recruit other proteins to create a repressive chromatin environment.
- Poly(A) binding protein: A trans-factor that binds to the poly(A) tail of mRNA and is involved in mRNA stability, translation, and localization. Examples of poly(A) binding proteins include the poly(A) binding protein 1 (PABP1) and the cytoplasmic poly(A) binding protein (PABPC1).
- RNA-binding protein: A trans-factor that binds to specific RNA sequences to regulate RNA processing, stability, and translation. Examples of RNA-binding proteins include the splicing factors, which bind to specific RNA sequences and regulate alternative splicing of pre-mRNA.
- RNA editing factor: A trans-factor that can modify RNA sequences by inserting, deleting, or changing nucleotides. Examples of RNA editing factors include the adenosine deaminases that act on RNA (ADARs) and the RNA editing enzyme APOBEC1.
- RNA editing enzyme: A trans-factor that can modify RNA sequences after transcription to generate alternative RNA isoforms. Examples of RNA editing enzymes include the adenosine deaminases that act on RNA (ADARs) and the apolipoprotein B mRNA editing enzyme catalytic subunit (APOBEC) family of proteins.
- RNA export factor: A trans-factor that is involved in the export of mRNA from the nucleus to the cytoplasm. Examples of RNA export factors include the nuclear export factor 1 (NXF1) and the RNA export factor 1 (REF1).
- RNA helicase: A trans-factor that can unwind RNA secondary structures to facilitate RNA processing and translation. Examples of RNA helicases include the DEAD-box proteins and the eIF4A protein.
- RNA interference (RNAi) factor: A trans-factor that is involved in the RNAi pathway, which regulates gene expression by degrading or blocking the translation of specific mRNAs. Examples of RNAi factors include the Dicer and Argonaute proteins.
- RNA polymerase: A trans-factor that catalyzes the synthesis of RNA from a DNA template. RNA polymerase is recruited to the promoter region of a gene by transcription factors and other regulatory proteins.
- Transcription factor: A trans-factor that binds to specific cis-elements to activate or repress transcription. Examples of transcription factors include the steroid hormone receptors, which bind to specific DNA sequences and regulate gene expression in response to hormone signaling.
- Transcriptional co-activator: A trans-factor that interacts with transcription factors and the basal transcriptional machinery to enhance transcription. Examples of transcriptional co-activators include the p300/CBP family of proteins.
- Transcriptional co-repressor: A trans-factor that interacts with transcription factors and other regulatory proteins to inhibit transcription. Examples of transcriptional co-repressors include the nuclear receptor co-repressor (NCoR) and the silencing mediator of retinoic acid and thyroid hormone receptors (SMRT).
- Transcriptional enhancer factor: A trans-factor that binds to enhancer elements to activate transcription. Examples of transcriptional enhancer factors include the E2F family of proteins and the AP-1 transcription factor complex.
- Transcriptional elongation factor: A trans-factor that is involved in the regulation of transcriptional elongation, which is the process of synthesizing RNA from a DNA template. Examples of transcriptional elongation factors include the positive transcription elongation factor b (P-TEFb) and the elongation factor SPT6.
- Transcriptional repressor: A trans-factor that binds to specific cis-elements to inhibit transcription. Examples of transcriptional repressors include the Krüppel-like zinc finger proteins and the Groucho/TLE family of proteins.
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CpG islands (CGIs) are regions of the genome that contain a large number of CpG dinucleotide repeats. In mammalian genomes, CpG islands usually extend for 300–3000 base pairs. They are located within and close to sites of about 40% of mammalian gene promoters.
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CpG islands are regions of DNA that are rich in CpG dinucleotides, which are cytosine nucleotides followed by guanine nucleotides. CpG islands play an important role in gene regulation, as they are often located near gene promoters and can affect gene expression.
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Aberrant methylation of CpG islands has been implicated in a number of diseases, including cancer. In cancer cells, CpG islands near tumor suppressor genes can become hypermethylated, leading to the inactivation of these genes and the promotion of tumor growth.
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Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosines. Enzymes that add a methyl group are called DNA methyltransferases. In mammals, 70% to 80% of CpG cytosines are methylated. Methylated cytosines often mutate to thymines.
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In humans, about 70% of promoters located near the transcription start site of a gene (proximal promoters) contain a CpG island.