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bioRxiv · 10.64898/2026.06.10.731474

Sequence-encoded H2A.Z nucleosome dynamics control DNA unwrapping and SUV420H1 recognition

Zhang, T.·Huang, L.·Li, X.·Liu, B.·Li, J.·Shi, C.·Fu, S.·Zhou, Z.·Xiang, S.
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Abstract

H2A.Z and canonical H2A adopt nearly identical nucleosomal folds, yet their distinct chromatin functions are not captured by static structural analysis. Using fast magic-angle spinning 1H-detected solid-state NMR, we show that H2A.Z possesses enhanced backbone flexibility in the L1 loop and the 2-L2 region (M2) relative to H2A. Chimeric segment-swapping demonstrates that these dynamic signatures are locally sequence-encoded and functionally transplantable. The inherent mobility of the M2 region promotes nucleosomal DNA-end unwrapping and persists when DNA ends are stabilized by linker histone H1 or opened by SUV420H1, indicating that this mobility is intrinsic rather than a passive consequence of DNA detachment. Chemical shift perturbation mapping and catalytic assays further show that SUV420H1 reads this H2A.Z-specific conformational landscape: the M2 region, together with the H2A.Z DS motif, supports variant-selective methyltransferase activity. These findings establish an axis of sequence-dynamics-accessibility-recognition along which local backbone fluctuations serve as physical determinants of epigenetic enzyme specificity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/731474v1_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@a50ceforg.highwire.dtl.DTLVardef@1f43af0org.highwire.dtl.DTLVardef@14969b8org.highwire.dtl.DTLVardef@bbbe0d_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Zhang, T., Huang, L., Li, X., Liu, B., Li, J., Shi, C., Fu, S., Zhou, Z., Xiang, S.. 2026-06-11. Sequence-encoded H2A.Z nucleosome dynamics control DNA unwrapping and SUV420H1 recognition. https://doi.org/10.64898/2026.06.10.731474

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