Reactome | PWWP2A, PWWP2B bind HDAC1,2:MTA1,MTA2,MTA3:RPPB4,RPPB7

PWWP2A, PWWP2B bind HDAC1,2:MTA1,MTA2,MTA3:RPPB4,RPPB7

Stable Identifier

R-HSA-9938437

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

3/5

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PWWP2A, PWWP2B bind HDAC1,2:MTA1,MTA2,MTA3:RPPB4,RPPB7

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PWWP2A and PWWP2B are chromatin-binding proteins that bind to H3K36me3, a histone mark associated with gene bodies of actively transcribed genes (Zhang et al, 2018; Link et al, 2018). PWWP2A/B also interact with H2A.Z-containing nucleosomes (a mark enriched at transcriptional start sites) and with H3K27Ac (Link et al, 2018; Zhang et al, 2018).
PWWP2A and PWWP2B interact with the MTA:HDAC:RBBP core and preclude recruitment of MBD, GATA2D and CHD proteins to the NuRD complex (Zhang et al, 2018; Link et al, 2018; reviewed in Reid et al, 2023). Binding of PWWP2A/B appears to be mediated by a R/QPRQV/L motif in the N-terminal region that interacts with MTA1, 2, or 3, with an apparent preference for MTA1 (Zhang et al, 2018; Link et al, 2018). MBD2/3 proteins contain a similar motif, suggesting that PWWP2A/B may compete with MBD2/3 for binding to the NuRD core. Consistent with this model of mutually exclusive binding, co-expression studies with MTA1, HDAC1, MBD3 and PWWP2A in HEK293 cells yielded two distinct complexes; PWWP2A:MTA1:HDAC1 and MBD3:MTA1:HDAC1 (Zhang et al, 2018).
The PWWP2A/B MTA:HDAC complex is enzymatically active, and knockout of PWWP2A/B increases H3K9Ac, H3K27Ac and H2A.ZAc on highly expressed genes (Link et al, 2018; Zhang et al, 2018).

Literature References

PubMed ID	Title	Journal	Year
30228260	A variant NuRD complex containing PWWP2A/B excludes MBD2/3 to regulate transcription at active genes Zhang, T, Wei, G, Millard, CJ, Fischer, R, Konietzny, R, Kessler, BM, Schwabe, JWR, Brockdorff, N	Nat Commun	2018
35798615	A NuRD for all seasons Reid, XJ, Low, JKK, Mackay, JP	Trends Biochem Sci	2023
30327463	PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex Link, S, Spitzer, RMM, Sana, M, Torrado, M, Völker-Albert, MC, Keilhauer, EC, Burgold, T, Pünzeler, S, Low, JKK, Lindström, I, Nist, A, Regnard, C, Stiewe, T, Hendrich, B, Imhof, A, Mann, M, Mackay, JP, Bartkuhn, M, Hake, SB	Nat Commun	2018