Reactome | Formation of the MLL4 complex

Formation of the MLL4 complex

Stable Identifier

R-HSA-9676268

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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KMT2D (also known as MLL4) binds the WRAD complex, consisting of WDR5, RBBP5, ASH2L and DPY30, to form the MLL4 complex. WDR5 plays an important role in the optimal stimulation of MLL4 methyltransferase activity by the RBBP5:ASH2L heterodimer (Zhang et al. 2012).

KMT2C and KMT2D are paralogous histone methyltransferases and mainly responsible for H3K4 mono-methylation (H3K4me1) at enhancers (Lee et al. 2013). KMT2D has a partial functional redundancy with KMT2C in cells, although the phenotypes of KMT2D and KMT2C null mice suggest that MLL4 might be the dominant counterpart (Lee et al. 2013). KMT2C/D are thought to play a role in the recruitment of the acetyltransferase CBP/p300 complex, which facilitates H3K27 acetylation and RNA polymerase II's recruitment to enhancer regions (Jin et al. 2011, Wang et al. 2016, Lai et al. 2017).

Literature References

PubMed ID	Title	Journal	Year
22266653	The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases Couture, JF, Brunzelle, JS, Zhang, P, Lee, H	Nucleic Acids Res.	2012
28398509	MLL3/MLL4 are required for CBP/p300 binding on enhancers and super-enhancer formation in brown adipogenesis Ge, K, Wang, L, Jang, Y, Lee, JE, Lai, B, Peng, W	Nucleic Acids Res	2017
24368734	H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation Ge, K, Zhuang, L, Wang, C, Wang, L, Baldridge, A, Lee, JE, Feng, X, Sartorelli, V, Cho, YW, Xu, S, Peng, W	Elife	2013
21131905	Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation Ge, K, Wang, C, Wang, L, Brindle, PK, Lee, JE, Kasper, LH, Yu, LR, Dent, SY, Jin, Q, Zhang, Z	EMBO J	2011
27698142	Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition Ge, K, Zhuang, L, Liu, C, Macfarlan, TS, Wang, C, Lee, JE, Lai, B, Xu, S, Peng, W	Proc Natl Acad Sci U S A	2016