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TitleImpacts of DNA methylation on H2A.Z deposition and nucleosome stability.
Journal, issue, pagesElife, Vol. 15, Year 2026
Publish dateJul 7, 2026
AuthorsRochelle M Shih / Yasuhiro Arimura / Hide A Konishi / Hironori Funabiki /
PubMed AbstractThe histone variant H2A.Z and DNA methylation are enriched at mutually exclusive genomic segments, though its mechanistic bases remain unclear. Here, we examine DNA methylation's influence on the ...The histone variant H2A.Z and DNA methylation are enriched at mutually exclusive genomic segments, though its mechanistic bases remain unclear. Here, we examine DNA methylation's influence on the intrinsic stability of the H2A.Z nucleosome and chaperone-mediated H2A.Z deposition. Cryo-EM and endonuclease analyses suggest that DNA methylation subtly increases the openness and accessibility of the H2A.Z nucleosome on satellite II-derived DNA sequences. In transcriptionally silent egg extracts, H2A.Z preferentially associates with unmethylated DNA though a substantial proportion of H2A.Z is recruited to methylated DNA. Preferential H2A.Z deposition to unmethylated DNA depends on the SRCAP complex, whose DNA binding is suppressed by methylation, while an SRCAP-independent and DNA methylation-insensitive mechanism for H2A.Z deposition also exists. Altogether, we propose that SRCAP drives the biased association of H2A.Z to unmethylated DNA, while additional mechanisms, potentially taking advantage of the subtle DNA methylation-induced physical effects, further assist the exclusion of H2A.Z from methylated DNA.
External linksElife / PubMed:42411467 / PubMed Central
MethodsEM (single particle)
Resolution2.78 - 3.14 Å
Structure data

70473

9ogr

9oh0

EMDB-70473: Cryo-EM analysis of human H2A.Z on methylated Sat2R-P DNA
PDB-9ogr: Cryo-EM analysis of human H2A.Z on methylated Sat2R-P DNA (v1)
PDB-9oh0: Cryo-EM analysis of human H2A.Z on methylated Sat2R-P DNA (v2)
Method: EM (single particle) / Resolution: 2.78 Å

70474

9ogs

9ogz

EMDB-70474, PDB-9ogs:
Cryo-EM analysis of human H2A.Z on Sat2R-P DNA (v1)
PDB-9ogz: Cryo-EM analysis of human H2A.Z on Sat2R-P DNA (v2)
Method: EM (single particle) / Resolution: 3.05 Å

70480

9oh1

EMDB-70480, PDB-9oh1:
Cryo-EM analysis of human H2A.Z on 601L DNA
Method: EM (single particle) / Resolution: 3.09 Å

70481

9oh2

EMDB-70481, PDB-9oh2:
Cryo-EM analysis of human H2A.Z on methylated 601L DNA
Method: EM (single particle) / Resolution: 3.14 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsDNA BINDING PROTEIN / Nucleosome / H2A.Z / DNA methylation

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