Molecular basis and specificity of H2A.Z–H2B recognition and deposition by the histone chaperone YL1

Abstract

H2A.Z, a widely conserved histone variant, is evicted from chromatin by the histone chaperone ANP32E. However, to date, no deposition chaperone for H2A.Z is known in metazoans. Here, we identify YL1 as a specific H2A.Z-deposition chaperone. The 2.7-Å-resolution crystal structure of the human YL1-H2A.Z-H2B complex shows that YL1 binding, similarly to ANP32E binding, triggers an extension of the H2A.Z αC helix. The interaction with YL1 is, however, more extensive and includes both the extended acidic patch and the entire DNA-binding surface of H2A.Z-H2B. Substitution of only four amino acid residues of H2A is sufficient for the formation of an H2A.Z-like interface specifically recognized by YL1. Collectively, our data reveal the molecular basis of H2A.Z-specific recognition by YL1 and shed light on the mechanism of H2A.Z transfer to the nucleosome by the ATP-dependent chromatin-remodeling complexes SRCAP and P400-TIP60.

Histone chaperone networks shaping chromatin function

“…The dynamics of the H2A docking domain, which supports the H3 αN helix in the nucleosome 65 , may also be under the control of histone chaperones. When bound by Swr1, ANP32E and YL1, an extra helical turn is observed in the carboxy-terminal helix of H2A.Z, which could potentially affect the trajectory of the H2A.Z docking domain 67–71 (FIG. 2Cd).…”

“…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.…”