[Recensão a] Thomas, D., Fowler, S., &amp; Johnson, V. (2017) - The Silence of the Archive.

Corujo, Luis

doi:10.14195/2182-7974_31_1_7

Cited by 1 publication

(2 citation statements)

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“…In this case, the ability of the variant to inhibit poly-ADP ribosylation by PARP1 would likely be affected by the stoichiometry of present macro domains, as well as their species. 23,25,51 Luger and Chakravarthy also observed that macroH2A and hybrid constructs, to a lesser extent, were resistant to exchange of dimers with the nucleosome assembly protein 1 (NAP1). In isolation of this information, our energetic analysis would suggest that the hybrid NCP should be the most resistant to this exchange, as the complex is the most stable.…”

Section: Discussionmentioning

confidence: 99%

“…13 Because of its involvement in transcriptional repression, macroH2A enrichment and depletion have been linked to regulation of pluripotent and cancerous cells. 25,26 While the effects of macroH2A substitution continue to be studied, there has been very little focus on the necessary quantities of macroH2A required to invoke each of these observed mechanisms. That is to say, do both dimers need to be substituted with macroH2A, or is the replacement of a single dimer sufficient?…”

Section: Introductionmentioning

confidence: 99%

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Unique Dynamics in Asymmetric macroH2A–H2A Hybrid Nucleosomes Result in Increased Complex Stability

2018

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The fundamental unit of eukaryotic chromatin is the nucleosome core particle, a protein/DNA complex that binds ~147 base pairs of DNA to a histone octamer. These histones-H3, H4, H2A,H2B-form the nucleosome core through a stacked interaction in which two H2A−H2B dimers flank the (H3−H4) 2 tetramer. In vivo, genetic accessibility can be modulated by the substitution of canonical histones with variant proteins that contain the same structural motif but a different amino acid sequence, such as the transcriptional repression-associated macroH2A variant. Previously, Chakravarthy and Luger published a crystal study that showed that H2A substitution is not necessarily required of both H2A moieties, but that in vitro recombination of nucleosomes in the presence of both macroH2A and H2A histone folds results in a hybrid macroH2A− H2A nucleosome with one dimer of each type. Here, we present molecular dynamics simulations of this hybrid construct and compare the results to our previous study on homogeneous H2A-and macroH2A-containing nucleosomes. We find that the hybrid contains a unique set of dynamics that stabilize the interactions between protein constituents and create an altogether more stable nucleosome, both in terms of protein−DNA and protein−protein binding. While dimer−tetramer interactions are asymmetric, as the difference in moieties would suggest, we observe that it is the canonical dimer that is pulled further into the nucleosome core, resulting in more secure dimer−tetramer bonds and a more stable histone core, and we also find significantly more interaction between the dimer subunits. Together, these models provide evidence for hybrid H2A−macroH2A nucleosome formation being not only possible but actually energetically more favorable than a homogeneous construct, with dynamics that are unique from their homogeneous H2A or macroH2A nucleosome counterparts. These effects of hybrid substitution likely propagate into higher-order chromatin structures to hinder transcriptional activity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%