KAT8 explained

K(lysine) acetyltransferase 8 (KAT8) is an enzyme that in humans is encoded by the KAT8 gene.^{[1] [2]}

Function

The MYST family of histone acetyltransferases, which includes KAT8, was named for the founding members MOZ (MYST3; MIM 601408), yeast YBF2 and SAS2, and TIP60 (HTATIP; MIM 601409). All members of this family contain a MYST region of about 240 amino acids with a canonical acetyl-CoA-binding site and a C2HC-type zinc finger motif. Most MYST proteins also have a chromodomain involved in protein-protein interactions and targeting transcriptional regulators to chromatin.

KAT8 is also known as MOF, and in humans hMOF. Given its fundamental role in modulating higher-order chromatin structure, hMOF is involved in many of the steps of the DNA damage response.^[3] The human hMOF gene encodes an enzyme that specifically acetylates histone H4 at lysine 16.^[3] The depletion of hMOF greatly decreases DNA double-strand break repair by both non-homologous end joining and homologous recombination.^[4] Thus MOF activity is critical for double-strand break repair.^[4]

Interactions

KAT8 has been shown to interact with MORF4L1.^[5]

Further reading

• Rea S, Xouri G, Akhtar A . Males absent on the first (MOF): from flies to humans . Oncogene . 26 . 37 . 5385–94 . August 2007 . 17694080 . 10.1038/sj.onc.1210607 . 12302768 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M . Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein . The EMBO Journal . 20 . 24 . 7184–96 . December 2001 . 11742995 . 125775 . 10.1093/emboj/20.24.7184 .
• Pelletier N, Champagne N, Stifani S, Yang XJ . MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2 . Oncogene . 21 . 17 . 2729–40 . April 2002 . 11965546 . 10.1038/sj.onc.1205367 . 19597517 .
• Pardo PS, Leung JK, Lucchesi JC, Pereira-Smith OM . MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation . The Journal of Biological Chemistry . 277 . 52 . 50860–6 . December 2002 . 12397079 . 10.1074/jbc.M203839200 . free .
• Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J . Large-scale cDNA transfection screening for genes related to cancer development and progression . Proceedings of the National Academy of Sciences of the United States of America . 101 . 44 . 15724–9 . November 2004 . 15498874 . 524842 . 10.1073/pnas.0404089101 . 2004PNAS..10115724W . free .
• Gupta A, Sharma GG, Young CS, Agarwal M, Smith ER, Paull TT, Lucchesi JC, Khanna KK, Ludwig T, Pandita TK . Involvement of human MOF in ATM function . Molecular and Cellular Biology . 25 . 12 . 5292–5305 . June 2005 . 15923642 . 1140595 . 10.1128/MCB.25.12.5292-5305.2005 .
• Dou Y, Milne TA, Tackett AJ, Smith ER, Fukuda A, Wysocka J, Allis CD, Chait BT, Hess JL, Roeder RG . Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF . Cell . 121 . 6 . 873–85 . June 2005 . 15960975 . 10.1016/j.cell.2005.04.031 . 14717470 . free .
• Taipale M, Rea S, Richter K, Vilar A, Lichter P, Imhof A, Akhtar A . hMOF histone acetyltransferase is required for histone H4 lysine 16 acetylation in mammalian cells . Molecular and Cellular Biology . 25 . 15 . 6798–810 . August 2005 . 16024812 . 1190338 . 10.1128/MCB.25.15.6798-6810.2005 .
• Cereseto A, Manganaro L, Gutierrez MI, Terreni M, Fittipaldi A, Lusic M, Marcello A, Giacca M . Acetylation of HIV-1 integrase by p300 regulates viral integration . The EMBO Journal . 24 . 17 . 3070–81 . September 2005 . 16096645 . 1201351 . 10.1038/sj.emboj.7600770 .
• Smith ER, Cayrou C, Huang R, Lane WS, Côté J, Lucchesi JC . A human protein complex homologous to the Drosophila MSL complex is responsible for the majority of histone H4 acetylation at lysine 16 . Molecular and Cellular Biology . 25 . 21 . 9175–88 . Nov 2005 . 16227571 . 1265810 . 10.1128/MCB.25.21.9175-9188.2005 .
• Topper M, Luo Y, Zhadina M, Mohammed K, Smith L, Muesing MA . Posttranslational acetylation of the human immunodeficiency virus type 1 integrase carboxyl-terminal domain is dispensable for viral replication . Journal of Virology . 81 . 6 . 3012–7 . March 2007 . 17182677 . 1865993 . 10.1128/JVI.02257-06 .

Notes and References

1. Neal KC, Pannuti A, Smith ER, Lucchesi JC . A new human member of the MYST family of histone acetyl transferases with high sequence similarity to Drosophila MOF . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1490 . 1–2 . 170–4 . Jan 2000 . 10786633 . 10.1016/s0167-4781(99)00211-0 .
2. Web site: Entrez Gene: MYST1 MYST histone acetyltransferase 1.
3. Chen QY, Costa M, Sun H . Structure and function of histone acetyltransferase MOF . AIMS Biophys . 2 . 4 . 555–569 . 2015 . 28503659 . 5425159 . 10.3934/biophy.2015.4.555 .
4. Sharma GG, So S, Gupta A, Kumar R, Cayrou C, Avvakumov N, Bhadra U, Pandita RK, Porteus MH, Chen DJ, Cote J, Pandita TK . MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair . Mol Cell Biol . 30 . 14 . 3582–95 . July 2010 . 20479123 . 2897562 . 10.1128/MCB.01476-09 .
5. Pardo PS, Leung JK, Lucchesi JC, Pereira-Smith OM . MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation . The Journal of Biological Chemistry . 277 . 52 . 50860–6 . Dec 2002 . 12397079 . 10.1074/jbc.M203839200 . free .