4dnc

Structural highlights

Function

[KAT8_HUMAN] Histone acetyltransferase which may be involved in transcriptional activation. May influence the function of ATM. As part of the MSL complex it is involved in acetylation of nucleosomal histone H4 producing specifically H4K16ac. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. That activity is less specific than the one of the MSL complex.^{[1] [2] [3]} [MSL1_HUMAN] Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at 'Lys-16' (H4K16ac) which is implicated in the formation of higher-order chromatin structure. Greatly enhances MSL2 E3 ubiquitin ligase activity, promoting monoubiquitination of histone H2B at 'Lys-34' (H2BK34Ub). This modification in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1. In the MSL complex, acts as a scaffold to tether MSL3 and KAT8 together for enzymatic activity regulation.^{[4] [5] [6]}

See Also

• Histone acetyltransferase

References

1. ↑ 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. J Biol Chem. 2002 Dec 27;277(52):50860-6. Epub 2002 Oct 22. PMID:12397079 doi:10.1074/jbc.M203839200
2. ↑ 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. Mol Cell Biol. 2005 Jun;25(12):5292-305. PMID:15923642 doi:25/12/5292
3. ↑ Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC. Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex. J Biol Chem. 2010 Feb 12;285(7):4268-72. doi: 10.1074/jbc.C109.087981. Epub 2009 , Dec 14. PMID:20018852 doi:10.1074/jbc.C109.087981
4. ↑ Smith ER, Cayrou C, Huang R, Lane WS, Cote 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. Mol Cell Biol. 2005 Nov;25(21):9175-88. PMID:16227571 doi:10.1128/MCB.25.21.9175-9188.2005
5. ↑ Wu L, Zee BM, Wang Y, Garcia BA, Dou Y. The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation. Mol Cell. 2011 Jul 8;43(1):132-44. doi: 10.1016/j.molcel.2011.05.015. PMID:21726816 doi:http://dx.doi.org/10.1016/j.molcel.2011.05.015
6. ↑ Huang J, Wan B, Wu L, Yang Y, Dou Y, Lei M. Structural insight into the regulation of MOF in the male-specific lethal complex and the non-specific lethal complex. Cell Res. 2012 Jun;22(6):1078-81. doi: 10.1038/cr.2012.72. Epub 2012 May 1. PMID:22547026 doi:10.1038/cr.2012.72