| ELP4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | ELP4 , AN, C11orf19, PAX6NEB, PAXNEB, dJ68P15A.1, helongator acetyltransferase complex subunit 4, AN2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 606985 MGI: 1925016 HomoloGene: 32433 GeneCards: ELP4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Elongation protein 4 homolog (S. cerevisiae), also known as ELP4, is a protein which in humans is encoded by the ELP4 gene. [5] [6] [7]
This gene encodes a component of the six subunit elongator complex, a histone acetyltransferase complex that associates directly with RNA polymerase II during transcriptional elongation. The human gene can partially complement sensitivity phenotypes of yeast ELP4 deletion mutants. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [5]
In a study published in February 2009, researcher linked this gene to the most common form of human epilepsy, namely Rolandic epilepsy. [8] This is the first gene to be linked with rolandic epilepsy.
It has been found that children with Rolandic epilepsy have a mutation of gene coding for the Elongator Protein Complex 4, which is involved in transcription and tRNA modification. Furthermore, Elp4 is needed for histone acetyltransferase (HAT) activity which makes DNA more accessible for transcription. The lack of the Elp4/5/6 led to no HAT activity. The importance of HAT activity is the initiation of transcription as well as its assistance of RNA polymerase II in transcription elongation through chromatin and acetyl-CoA dependent pathways. [9] Although Rolandic epilepsy (RE), which has been observed as autosomal dominant with high penetrance, [10] develops around age 3 and disappears by age 12 there are serious problems that need to be addressed that occur while a child has RE. One of the major problems that can arise from RE is cognitive impairment. Though the cognitive impairment seen in Rolandic Epilepsy is of unclear etiology, one contributing factor may be increased glucose uptake in cortical areas, most notably in the associative cortex. [11] These changes in glucose uptake may somehow disrupt the learning process and prevents the child from making the associations necessary to learn new things, which is how most human learning is achieved. Other factors which may contribute to cognitive impairment include seizure frequency, abnormal electrical activity in between seizures, and medication side effects, to only name a few.
The Elongator Protein Complex (ELP) is what regulates the growth of cortical projection neurons. This means that it helps cortical neurons to exhibit dendrite branching and radial migration of neurons to form the close knit neural network of the cerebral cortex. [12] If ELP is not working properly or is not being expressed at the correct levels (too low) then the neurons in that region in particular would not be properly situated in relation to each other for proper brain activity. The expression of ELP and the fourth sub-unit (ELP4) in particular is the cause of Rolandic epilepsy and possibly other cognitive impairment later in life if the condition is severe enough or if it is not treated effectively.
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.
In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from altering the number of copies of RNA that are transcribed, to the temporal control of when the gene is transcribed. This control allows the cell or organism to respond to a variety of intra- and extracellular signals and thus mount a response. Some examples of this include producing the mRNA that encode enzymes to adapt to a change in a food source, producing the gene products involved in cell cycle specific activities, and producing the gene products responsible for cellular differentiation in multicellular eukaryotes, as studied in evolutionary developmental biology.
IKBKAP is a human gene encoding the IKAP protein, which is ubiquitously expressed at varying levels in all tissue types, including brain cells. The IKAP protein is thought to participate as a sub-unit in the assembly of a six-protein putative human holo-Elongator complex, which allows for transcriptional elongation by RNA polymerase II. Further evidence has implicated the IKAP protein as being critical in neuronal development, and directs that decreased expression of IKAP in certain cell types is the molecular basis for the severe, neurodevelopmental disorder familial dysautonomia. Other pathways that have been connected to IKAP protein function in a variety of organisms include tRNA modification, cell motility, and cytosolic stress signalling. Homologs of the IKBKAP gene have been identified in multiple other Eukaryotic model organisms. Notable homologs include Elp1 in yeast, Ikbkap in mice, and D-elp1 in fruit flies. The fruit fly homolog (D-elp1) has RNA-dependent RNA polymerase activity and is involved in RNA interference.
Eukaryotic transcription is the elaborate process that eukaryotic cells use to copy genetic information stored in DNA into units of transportable complementary RNA replica. Gene transcription occurs in both eukaryotic and prokaryotic cells. Unlike prokaryotic RNA polymerase that initiates the transcription of all different types of RNA, RNA polymerase in eukaryotes comes in three variations, each translating a different type of gene. A eukaryotic cell has a nucleus that separates the processes of transcription and translation. Eukaryotic transcription occurs within the nucleus where DNA is packaged into nucleosomes and higher order chromatin structures. The complexity of the eukaryotic genome necessitates a great variety and complexity of gene expression control.
Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.
Histone deacetylase 2 (HDAC2) is an enzyme that in humans is encoded by the HDAC2 gene. It belongs to the histone deacetylase class of enzymes responsible for the removal of acetyl groups from lysine residues at the N-terminal region of the core histones. As such, it plays an important role in gene expression by facilitating the formation of transcription repressor complexes and for this reason is often considered an important target for cancer therapy.
Paired amphipathic helix protein Sin3a is a protein that in humans is encoded by the SIN3A gene.
Histone-binding protein RBBP4 is a protein that in humans is encoded by the RBBP4 gene.
Methyl-CpG-binding domain protein 2 is a protein that in humans is encoded by the MBD2 gene.
Histone-binding protein RBBP7 is a protein that in humans is encoded by the RBBP7 gene.
Protein arginine N-methyltransferase 5 is an enzyme that in humans is encoded by the PRMT5 gene. PRMT5 symmetrically dimethylates H2AR3, H4R3, H3R2, and H3R8 in vivo, all of which are linked to a range of transcriptional regulatory events.
Methyl-CpG-binding domain protein 3 is a protein that in humans is encoded by the MBD3 gene.
Sin3A-associated protein, 30kDa, also known as SAP30, is a protein which in humans is encoded by the SAP30 gene.
RNA polymerase II subunit A C-terminal domain phosphatase is an enzyme that in humans is encoded by the CTDP1 gene.
Mediator of RNA polymerase II transcription subunit 6 is one of the subunits of the Mediator complex. It is an enzyme that in humans is encoded by the MED6 gene.
Mediator of RNA polymerase II transcription subunit 4 also known as mediator complex subunit 4 (MED4), a component of Mediator or vitamin D3 receptor-interacting protein complex 36 kDa component (DRIP36) is a protein that in humans is encoded by the MED4 gene.
Elongator complex protein 3, also named KAT9, is a protein that in humans is encoded by the ELP3 gene. ELP3 is the catalytic histone acetyltransferase subunit of the RNA polymerase II elongator complex, which is a component of the RNA polymerase II holoenzyme and is involved in transcriptional elongation. ELP3 supports the migration and branching of projection neurons through acetylation of alpha-tubulin in the developing cerebral cortex. In mammals, ELP3 is important for paternal DNA demethylation after fertilization. ELP3 is potentially involved in cellular redox homeostasis by mediating the acetylation of glucose-6-phosphate dehydrogenase. Besides, ELP3 may play a role in chromatin remodeling and is involved in acetylation of histones H3 and probably H4.
Histone-lysine N-methyltransferase SETD7 is an enzyme that in humans is encoded by the SETD7 gene.
Histone deacetylase complex subunit SAP18 is an enzyme that in humans is encoded by the SAP18 gene.
Elongator complex protein 2 is a protein that in humans is encoded by the ELP2 gene.
