Abstract
Histone variants fine-tune transcription, replication, DNA damage repair, and faithful chromosome segregation. Whether and how nucleosome variants encode unique mechanical properties to their cognate chromatin structures remains elusive. Here, using in silico and in vitro nanoindentation methods, extending to in vivo dissections, we report that histone variant nucleosomes are intrinsically more elastic than their canonical counterparts. Furthermore, binding proteins, which discriminate between histone variant nucleosomes, suppress this innate elasticity and also compact chromatin. Interestingly, when we overexpress the binding proteins in vivo, we also observe increased compaction of chromatin enriched for histone variant nucleosomes, correlating with diminished access. Taken together, these data suggest a plausible link between innate mechanical properties possessed by histone variant nucleosomes, the adaptability of chromatin states in vivo, and the epigenetic plasticity of the underlying locus.
Highlights
Histone variants fine-tune transcription, replication, DNA damage repair, and faithful chromosome segregation
Another major paradox is that despite being buried in pericentric heterochromatin [13,14,15], CENP-A chromatin is transcriptionally active in most species, suggesting that this chromatin is accessible even when bound to kinetochore proteins [16, 17]
We found that the CENP-A nucleosome variant is more elastic than the canonical H3 nucleosome but becomes stiffer when bound to its partner CENP-C
Summary
Histone variants fine-tune transcription, replication, DNA damage repair, and faithful chromosome segregation. In contrast to the previous view that chromatin was a mostly static packaging polymer, several recent studies have unveiled a rich conformational landscape of nucleosomes [2] These works raise the intriguing possibility that mechanical properties embedded within evolutionarily distinct nucleosome types might lead to different structural outcomes for the chromatin fiber. Another major paradox is that despite being buried in pericentric heterochromatin [13,14,15], CENP-A chromatin is transcriptionally active in most species, suggesting that this chromatin is accessible even when bound to kinetochore proteins [16, 17] This puzzling dichotomy can be explained either by intrinsic mechanical properties or by epigenetic alterations driven by chromatin effectors. We report that the smallest unit of the chromatin fiber can have profound effects on the 3D folding properties of chromatin, with implications for the accessibility of that chromatin to the transcriptional machinery
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