Structural basis of H2A.Z recognition by SRCAP chromatin-remodeling subunit YL1

Abstract

Histone variant H2A.Z, a universal mark of dynamic nucleosomes flanking gene promoters and enhancers, is incorporated into chromatin by SRCAP (SWR1), an ATP-dependent, multicomponent chromatin-remodeling complex. The YL1 (Swc2) subunit of SRCAP (SWR1) plays an essential role in H2A.Z recognition, but how it achieves this has been unclear. Here, we report the crystal structure of the H2A.Z-binding domain of Drosophila melanogaster YL1 (dYL1-Z) in complex with an H2A.Z-H2B dimer at 1.9-Å resolution. The dYL1-Z domain adopts a new whip-like structure that wraps over H2A.Z-H2B, and preferential recognition is largely conferred by three residues in loop 2, the hyperacidic patch and the extended αC helix of H2A.Z. Importantly, this domain is essential for deposition of budding yeast H2A.Z in vivo and SRCAP (SWR1)-catalyzed histone H2A.Z replacement in vitro. Our studies distinguish YL1-Z from known H2A.Z chaperones and suggest a hierarchical mechanism based on increasing binding affinity facilitating H2A.Z transfer from SRCAP (SWR1) to the nucleosome.

Histone chaperone networks shaping chromatin function

“…33), Chz1 (REF. 82) and YL1 (REFS 70,71) (FIG. 2) imply that the chaper-one undergoes a marked transformation upon histone binding.…”

“…55), Chz1 (REF. 106), ANP32E 68,69 , YL1 (REFS 70,71) and FACT 36 . Nap1 is a multifunctional chaperone that shields the DNA-binding interfaces of histones 52 and prevents unscheduled accumulation of H2A–H2B on DNA 19 .…”

“…Furthermore, if Chz1 and Nap1 are absent, FACT is able to substitute these two chaperones to compensate and deliver H2A.Z–H2B to the Swr1 remodelling complex (SWR-C) for deposition 106 . In human cells, H2A.Z–H2B is handled by the variant-specific chaperones ANP32E 68,69 and YL1 (REFS 70,71); of these two Swr1-related complexes in mammals, YL1 functions in both SRCAP and P400–TIP60 (REF. 127), whereas ANP32E seems to be specific for p400–TIP60 (REF.…”

“…This process involves two distinct chaperone activities of SWR-C, provided by the catalytic subunit Swr1 (REFS 67,172) and the accessory subunit Swc2 (REF. 171) (YL1 (REFS 70,71)). Interestingly SWR-C function is directed to nucleosomes flanking the transcription start site due to the preference of SWR-C for nucleosomes with long linker DNA 175,176 , which is exposed in the nucleosome-free region (FIG.…”

“…B. Histone chaperones binding tetrameric H3–H4: (part Ba ) MCM2–H3–H4 (PDB ID: 5BNV) 34 — note that the structure includes two MCM2 HBDs; (part Bb ) SPT2–H3–H4 (PDB ID: 5BSA) 33 ; and (part Bc ) SPT16 middle domain (SPT16-M)–H3–H4 (PDB ID: 4Z2M) 37 . C. Histones chaperones binding dimeric H2A– or H2A.Z–H2B: (part Ca ) Nap1–H2A–H2B (PDB ID: 5G2E) 52 ; (part Cb ) minimal binding domain (MBD) of ANP32E (PDB ID: 4CAY, 4NFT) 68,69 and Swr1 (PDB ID: 4M6B) 67 with a H2A.Z–H2B chimaera (H2A.Z αC helix extension indicated), and SPT16 with H2A–H2B (PDB ID: 4WNN) 46 ; (part Cc ) SPT16-M–H2B chimaera with H2A (PDB ID: 4KHA) 41 ; (part Cd ) YL1 in complex with H2A.Z–H2B (PDB ID: 5FUG, 5CHL) 71,70 ; and (part Ce ) Chz1–H2A.Z–H2B (PDB ID: 2JSS) 82 . D. Co-chaperone complexes: (part Da ) MCM2–Asf1 chimaera bound to H3–H4 (PDB ID: 5BO0) 34 ; (part Db ) the Vps75–Asf1–H3–H4 co-chaperone complex 51 ; (part Dc ) UBN1–H3.3–H4–Asf1 (PDB ID: 4ZBJ) 93 ; and (part Dd ) MCM2-TONSL bound to a H3–H4 tetramer (PDB ID: 5JA4) 84 .…”