SETD2

SETD2 protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II.

The trimethylation of lysine-36 of histone H3 (H3K36me3) is required in human cells for homologous recombinational repair and genome stability.{{cite journal |vauthors=Pfister SX, Ahrabi S, Zalmas LP, Sarkar S, Aymard F, Bachrati CZ, Helleday T, Legube G, La Thangue NB, Porter AC, Humphrey TC |title=SETD2-dependent histone H3K36 trimethylation is required for homologous recombination repair and genome stability |journal=Cell Rep |volume=7 |issue=6 |pages=2006–18 |date=June 2014 |pmid=24931610 |pmc=4074340 |doi=10.1016/j.celrep.2014.05.026 }} Depletion of SETD2 increases the frequency of deletion mutations that arise by the alternative DNA repair process of microhomology-mediated end joining.

The SETD2 gene is located on the short arm of chromosome 3 and has been shown to play a tumour suppressor role in human cancer.{{cite journal | vauthors = Al Sarakbi W, Sasi W, Jiang WG, Roberts T, Newbold RF, Mokbel K | author6-link = kefah Mokbel | title = The mRNA expression of SETD2 in human breast cancer: correlation with clinico-pathological parameters | journal = BMC Cancer | volume = 9 | pages = 290 | year = 2009 | pmid = 19698110 | pmc = 3087337 | doi = 10.1186/1471-2407-9-290 | doi-access = free }}

SETD2 has been shown to interact with Huntingtin.{{cite journal | vauthors = Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME | title = Huntingtin interacts with a family of WW domain proteins | journal = Hum. Mol. Genet. | volume = 7 | issue = 9 | pages = 1463–74 |date=September 1998 | pmid = 9700202 | doi = 10.1093/hmg/7.9.1463 | doi-access = free }} Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. SETD2 belongs to a class of huntingtin interacting proteins characterized by WW motifs.

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