Structural dynamics of nucleosome mediated by acetylations at H3K56 and H3K115,122

Abstract

Post translational modifications have a profound role in the regulation of several biological processes such as transcription, replication, and DNA repair. Acetylation and phosphorylation form a major class of post translational modifications involved in nucleosomal regulation by modifying its structure. The effect of post translational modifications on nucleosome structure could be better explored when the molecular trajectories explaining the time dependent structural evolution over a period of time is examined at the atomic level. The present study attempts to highlight the importance of acetylation, especially at entry-exit (Lys56) and dyad (Lys115 and Lys122) regions in regulating the nucleosome accessibility and mobility using all atom simulations. It is evident from this study that acetylation at Lys56, Lys115, and Lys122 introduces local changes in the electrostatic nature of the lateral surface and thereby weakens the histone-DNA interactions. In addition, simulations also reveal significant changes in the dynamics of superhelical DNA. The acetylation at Lys56 promotes a high amplitude out-of-planar movement of entry-exit termini. Whereas, acetylation at Lys115 and Lys122 increases the flexibility of the superhelical DNA to facilitate the rolling of the superhelical DNA around the octameric histone. In essence, the present study highlights the role of acetylation at Lys56, Lys115, and Lys122 in transcriptional regulation by promoting high amplitude dynamics of superhelical DNA for a possible unwrapping as well as mobility of nucleosome.

Aspirin inhibits TGFβ2-induced epithelial to mesenchymal transition of lens epithelial cells: selective acetylation of K56 and K122 in histone H3

“…However, we found aspirin-mediated acetylation at K56 and K122, which are in the globular domain of H3. The modification of histones can affect two of their properties: the DNA binding affinity and the recruitment of nonhistone proteins [66,67]. The lateral side of histones regulates transcriptional activity [68].…”

H2A-H2B Histone Dimer Plasticity and Its Functional Implications

“…Among the arsenal of methods available to study nucleosome dynamics, molecular dynamics (MD) simulations have proven to be a useful tool, especially in combination with experimental methods such as NMR, cryo-EM, hydrogen-deuterium exchange, FRET, etc. All-atom MD simulations have been used to study histone tail dynamics [ 15 , 16 ], counter ion atmospheres [ 17 ], DNA wrapping/unwrapping [ 18 , 19 , 20 ], dynamics of sub-nucleosome particles [ 21 ], the effect of histone variants [ 22 , 23 , 24 , 25 ], histone post-translational modifications [ 26 , 27 , 28 ], DNA methylation [ 29 ], supra-nucleosome structures [ 30 ], etc. MD simulations can provide atomistic details about certain dynamical processes in nucleosomes and help to obtain mechanistic insights into the coupling between different dynamical modes.…”

A non-canonical histone acetyltransferase targets intragenic enhancers and regulates plant architecture

“…The dynamics of chromatin structure are strictly regulated by multiple mechanisms, including post-translational modification of histones 14,15 . Tail-based histone acetylation functions as docking sites for the recruitment of transcriptional regulators, whereas recent data suggest that acetylation of lysine residues, in the globular domain of histone H3 (H3K56 and H3K122), can directly alter histone – DNA interactions, thereby modulating chromatin architecture 16-18 and stimulating transcription 19-21 . In yeast, histone chaperone-dependent acetylation of H3K56, by the histone acetyltransferase (HAT) Rtt109, is required for chromatin assembly, during DNA replication 22-25 , and for chromatin disassembly during transcriptional activation 19,21 .…”