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PMID:26320581

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Citation

'Zhang, Y, Mittal, A, Reid, J, Reich, S, Gamblin, SJ and Wilson, JR (2015) Evolving Catalytic Properties of the MLL Family SET Domain. Structure '

Abstract

Methylation of histone H3 lysine-4 is a hallmark of chromatin associated with active gene expression. The activity of H3K4-specific modification enzymes, in higher eukaryotes the MLL (or KMT2) family, is tightly regulated. The MLL family has six members, each with a specialized function. All contain a catalytic SET domain that associates with a core multiprotein complex for activation. These SET domains segregate into three classes that correlate with the arrangement of targeting domains that populate the rest of the protein. Here we show that, unlike MLL1, the MLL4 SET domain retains significant activity without the core complex. We also present the crystal structure of an inactive MLL4-tagged SET domain construct and describe conformational changes that account for MLL4 intrinsic activity. Finally, our structure explains how the MLL SET domains are able to add multiple methyl groups to the target lysine, despite having the sequence characteristics of a classical monomethylase.

Links

PubMed Online version:10.1016/j.str.2015.07.018

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RBBP5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q91X20

F

Seeded From UniProt

complete

MOUSE:ASH2L

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8BX09

F

Seeded From UniProt

complete

HUMAN:KMT2D

GO:0097692: histone H3-K4 monomethylation

ECO:0000314:

P

Figure 6e

complete
CACAO 11125

HUMAN:KMT2D

GO:0051568: histone H3-K4 methylation

ECO:0000314:

P

Figure 6e

complete
CACAO 11070

HUMAN:KMT2D

GO:0042800: histone methyltransferase activity (H3-K4 specific)

ECO:0000314:

F

Figure 6e

complete
CACAO 11073

HUMAN:KMT2D

GO:0044648: histone H3-K4 dimethylation

ECO:0000314:

P

Figure 6e

complete
CACAO 11074

HUMAN:KMT2D

GO:0080182: histone H3-K4 trimethylation

ECO:0000314:

P

Figure 6e

complete
CACAO 11075

Notes

See also

References

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