ELP4

From Wikipedia, the free encyclopedia
ELP4
Identifiers
AliasesELP4, AN, C11orf19, PAX6NEB, PAXNEB, dJ68P15A.1, helongator acetyltransferase complex subunit 4, AN2
External IDsOMIM: 606985 MGI: 1925016 HomoloGene: 32433 GeneCards: ELP4
Orthologs
SpeciesHumanMouse
Entrez

26610

77766

Ensembl

ENSG00000109911

ENSMUSG00000027167

UniProt

Q96EB1

Q9ER73

RefSeq (mRNA)

NM_001288725
NM_001288726
NM_019040

NM_023876

RefSeq (protein)

NP_001275654
NP_001275655
NP_061913

NP_076365

Location (UCSC)Chr 11: 31.51 – 31.79 MbChr 2: 105.53 – 105.73 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

Function[]

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]

Clinical significance[]

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.

Background[]

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.

References[]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000109911 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027167 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: ELP4 elongation protein 4 homolog (S. cerevisiae)".
  6. ^ Winkler GS, Petrakis TG, Ethelberg S, Tokunaga M, Erdjument-Bromage H, Tempst P, Svejstrup JQ (August 2001). "RNA polymerase II elongator holoenzyme is composed of two discrete subcomplexes". J. Biol. Chem. 276 (35): 32743–9. doi:10.1074/jbc.M105303200. PMID 11435442.
  7. ^ Kleinjan DA, Seawright A, Elgar G, van Heyningen V (February 2002). "Characterization of a novel gene adjacent to PAX6, revealing synteny conservation with functional significance". Mamm. Genome. 13 (2): 102–7. doi:10.1007/s00335-001-3058-y. PMID 11889558. S2CID 23006323.
  8. ^ Strug LJ, Clarke T, Chiang T, et al. (January 2009). "Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4)". Eur. J. Hum. Genet. 17 (9): 1171–81. doi:10.1038/ejhg.2008.267. PMC 2729813. PMID 19172991.
  9. ^ Winkler GS, Kristjuhan A, Erdjument-Bromage H, Tempst P, Svejstrup JQ (March 2002). "Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo". Proc. Natl. Acad. Sci. U.S.A. 99 (6): 3517–22. doi:10.1073/pnas.022042899. PMC 122555. PMID 11904415.
  10. ^ Bali B, Kull LL, Strug LJ, Clarke T, Murphy PL, Akman CI, Greenberg DA, Pal DK (December 2007). "Autosomal Dominant Inheritance of Centrotemporal Sharp Waves in Rolandic Epilepsy Families". Epilepsia. 48 (12): 2266–72. doi:10.1111/j.1528-1167.2007.01221.x. PMC 2150739. PMID 17662063.
  11. ^ Strug LJ, Clarke T, Chiang T, Chien M, Baskurt Z, Li W, Dorfman R, Bali B, Wirrell E, Kugler SL, Mandelbaum DE, Wolf SM, McGoldrick P, Hardison H, Novotny EJ, Ju J, Greenberg DA, Russo JJ, Pal DK (January 2009). "Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4)". Eur. J. Hum. Genet. 17 (9): 1171–81. doi:10.1038/ejhg.2008.267. PMC 2729813. PMID 19172991.
  12. ^ Creppe C, Malinouskaya L, Volvert ML, Gillard M, Close P, Malaise O, Laguesse S, Cornez I, Rahmouni S, Ormenese S, Belachew S, Malgrange B, Chapelle JP, Siebenlist U, Moonen G, Chariot A, Nguyen L (February 2009). "Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin". Cell. 136 (3): 551–64. doi:10.1016/j.cell.2008.11.043. PMID 19185337. S2CID 18351772.

Further reading[]


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