| Structural highlights
Function
[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.[1] [2] [3] [MSL2_HUMAN] Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16 which is implicated in the formation of higher-order chromatin structure. Acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. This activity is greatly enhanced by heterodimerization with MSL1. H2B ubiquitination in turn stimulates histine H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1.[4]
Publication Abstract from PubMed
The Male-Specific Lethal (MSL) complex regulates dosage compensation of the male X chromosome in Drosophila. Here, we report the crystal structure of its MSL1/MSL2 core, where two MSL2 subunits bind to a dimer formed by two molecules of MSL1. Analysis of structure-based mutants revealed that MSL2 can only interact with the MSL1 dimer, but MSL1 dimerization is MSL2 independent. We show that Msl1 is a substrate for Msl2 E3 ubiquitin ligase activity. ChIP experiments revealed that Msl1 dimerization is essential for targeting and spreading of the MSL complex on X-linked genes; however, Msl1 binding to promoters of male and female cells is independent of the dimer status and other MSL proteins. Finally, we show that loss of Msl1 dimerization leads to male-specific lethality. We propose that Msl1-mediated dimerization of the entire MSL complex is required for Msl2 binding, X chromosome recognition, and spreading along the X chromosome.
Msl1-mediated dimerization of the dosage compensation complex is essential for male X-chromosome regulation in Drosophila.,Hallacli E, Lipp M, Georgiev P, Spielman C, Cusack S, Akhtar A, Kadlec J Mol Cell. 2012 Nov 30;48(4):587-600. doi: 10.1016/j.molcel.2012.09.014. Epub 2012, Oct 18. PMID:23084835[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ 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
- ↑ Hallacli E, Lipp M, Georgiev P, Spielman C, Cusack S, Akhtar A, Kadlec J. Msl1-mediated dimerization of the dosage compensation complex is essential for male X-chromosome regulation in Drosophila. Mol Cell. 2012 Nov 30;48(4):587-600. doi: 10.1016/j.molcel.2012.09.014. Epub 2012, Oct 18. PMID:23084835 doi:http://dx.doi.org/10.1016/j.molcel.2012.09.014
|
