| Structural highlights
6mlc is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Gene: | KMT2C, HALR, KIAA1506, MLL3 (HUMAN) |
| Activity: | Histone-lysine N-methyltransferase, with EC number 2.1.1.43 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[KMT2C_HUMAN] Histone methyltransferase. Methylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Central component of the MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. KMT2C/MLL3 may be a catalytic subunit of this complex. May be involved in leukemogenesis and developmental disorder.[1]
Publication Abstract from PubMed
MLL3 and MLL4 are two closely related members of the SET1/MLL family of histone H3K4 methyltransferases and are responsible for monomethylating histone H3K4 on enhancers, which are essential in regulating cell-type-specific gene expression. Mutations of MLL3 or MLL4 have been reported in different types of cancer. Recently, the PHD domains of MLL3/4 have been reported to recruit the MLL3/4 complexes to their target genes by binding to histone H4 during the NT2/D1 stem cell differentiation. Here we show that an extended PHD domain (ePHD6) involving the sixth PHD domain and its preceding zinc finger in MLL3 and MLL4 specifically recognizes an H4H18-containing histone H4 fragment and that modifications of residues surrounding H4H18 modulate H4 binding to MLL3/4. Our in vitro methyltransferase assays and cellular experiments further reveal that the interaction between ePHD6 of MLL3/4 and histone H4 is required for their nucleosomal methylation activity and MLL4-mediated neuronal differentiation of NT2/D1 cells.
Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4.,Liu Y, Qin S, Chen TY, Lei M, Dhar SS, Ho JC, Dong A, Loppnau P, Li Y, Lee MG, Min J Nat Commun. 2019 Jan 3;10(1):36. doi: 10.1038/s41467-018-07906-3. PMID:30604749[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cho YW, Hong T, Hong S, Guo H, Yu H, Kim D, Guszczynski T, Dressler GR, Copeland TD, Kalkum M, Ge K. PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex. J Biol Chem. 2007 Jul 13;282(28):20395-406. Epub 2007 May 11. PMID:17500065 doi:http://dx.doi.org/M701574200
- ↑ Liu Y, Qin S, Chen TY, Lei M, Dhar SS, Ho JC, Dong A, Loppnau P, Li Y, Lee MG, Min J. Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4. Nat Commun. 2019 Jan 3;10(1):36. doi: 10.1038/s41467-018-07906-3. PMID:30604749 doi:http://dx.doi.org/10.1038/s41467-018-07906-3
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