Table 1 KMT2C/D COMPASS complex components
A. Protein domains | |||
|---|---|---|---|
Domain | Interaction | Function | Protein Containing |
Plant homeodomains (PHD) | Histones | Serve as epigenetic readers by identifying and binding to post-translationally modified histones. | KMT2C/D |
Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) | WARD Complex, Histone 3 tail | Catalyzes the transfers of a methyl group from S-adenosyl-L-methionine (SAM) donor factor to the ε amino group of recipient lysine residues. | KMT2C/D, EHMT1 |
WDR5 interaction motif (WIM) | H3K4, WDR5 | Arginine-containing motif which binds WDR5 (via Phe133 /Phe263 residues) and facilitates protein-protein interaction. | KMT2C/D |
Kabuki interaction surface (KIS) | H3K4, WRAD complex | KMT2 protein surface near the SET domain which combines with WRAD proteins to forms a secondary active site. | KMT2C/D |
WDR5-interacting site (Win) | KMT2 proteins | Phenylalanine-containing site which binds KMT2 proteins via WIM. Also acts as H3R2me2 "reader" of poised genes. | WDR5 |
WDR5-binding motif (WBM) | RBBP5, NSL, NuRD, others | Facilitates binding of WDR5 to other proteins, including RBBP5 of the KMT2C/D COMPASS complex. | WDR5 |
WD40 motif (tryptophan-aspartic acid [W-D] dipeptide) | NA | Motif which forms a rigid circularized structure, facilitating protein-protein interactions in large protein complexes. | WDR5, RBBP5 |
Histone acetyltransferase (HAT) | H3K27, others | Catalyzes acetylation of lysine residues. Histone tail lysine acetylation is generally linked with transcriptional activation. | CBP, P300 |
B. COMPASS associated proteins | |||
Protein | Interaction | Function | |
WD repeat domain 5 (WDR5) | KMT2D, RBBP5 | Part of WARD complex; acts as a histone specific reader associated with chromatin “poised” for transcription. | |
Absent, small or homeotic 2-like (ASH2L) | KMT2D, RBBP5, DPY30 | Part of WARD complex; contains a histone-binding PHD and DNA-binding that provide docking sites for DPY-30. | |
Retinoblastoma binding protein 5 (RBBP5) | WDR5, ASH2L | Part of WARD complex; acts as a scaffold protein between ASH2L and WDR5. | |
Dumpy 30 (Methyltransferase complex regulatory subunit)(DPY30) | ASH2L, DPY30 | Part of WARD complex; small nuclear trans-golgi network protein involved in transcription, cell migration and endosomal trafficking. | |
Activating signal cointegrator-2 (ASC-2) | KMT2C/D, RAR | Co-activates and helps recruit KMT2C/D to nuclear receptors. | |
Creb binding protein (CBP) | UTX, RAR | Co-activates transcription factors and has intrinsic histone acetyltransferase activity. | |
Enzyme p300 (EP300 or P300) | UTX, RAR | Co-activates transcription factors and has intrinsic histone acetyltransferase activity. | |
PAX-interacting protein1-associated glutamate rich protein 1a (PA1) | PTIP | Stabilizes PTIP. | |
PAX-interacting protein 1 (PTIP) | KMT2C/D, PA1 | Involved in transcriptional regulation by binding various transcription factors, also has roles in DNA repair / progression through mitosis. | |
Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX/KDM6A) | KMT2C/D, RAR | Demethylates lysine 27 on histone 3, generally resulting activation of gene expression. | |