Biology subjects

YAMAMOTO, T.

Publications and source records attributed to YAMAMOTO, T..

3 recordsLinked to original sources

bioRxiv2021

Slow chromatin dynamics enhances promoter accessibility to transcriptional condensates

Enhancers are DNA sequences at a long genomic distance from target genes. Recent experiments suggest that enhancers are anchored to the surfaces of condensates of transcription machinery and that the loop extrusion process enhances the transcription level of their target genes. Here we theoretically study the polymer dynamics driven by the loop extrusion of the linker DNA between an enhancer and the promoter of its target gene to calculate the contact probability of the promoter to the transcription machinery in the condensate. Our theory predicts that when the loop extrusion process is active, the contact probability increases with increasing linker DNA length. This finding reflects the fact that the relaxation time, with which the promoter stays in proximity to the surface of the transcriptional condensate, increases as the length of the linker DNA increases. This contrasts the equilibrium case for which the contact probability between the promoter and the transcription machineries is smaller for longer linker DNA lengths.

biophysics↗

bioRxiv2020

Phase separation of chromatin brush driven by enzymatic reaction dynamics of histone posttranslational modifications

The nuclei of undifferentiated cells show uniform decompacted chromatin while during development nuclei decrease in size and foci of condensed chromatin appear, reminiscent of phase separation. This study is motivated by recent experiments that suggest that the unbinding of enzymes that chemically modify (acetylate) histone tails causes decompaction of condensed chromatin. Here we take into account the enzymatic reactions of histone modifications to predict the phase separation of chromatin in a model system, the chromatin brush, which mimics chromatin at the proximity of a nuclear membrane. The model contains activators and silencers, which change the state of the nucleosomes to (transcriptionally) active or inactive via the Michaelis-Menten kinetics. Our theory predicts that the chromatin brush will phase separate when the brush height is reduced below a threshold height. The phase separation is driven by an anti-correlation: Activators change the state of nucleosomes to the active state suppressing the binding of silencers to these nucleosomes and vice versa.

biophysics↗

bioRxiv2020

Triblock copolymer micelle model of spherical paraspeckles

Paraspeckles are nuclear bodies composed of architectural RNA (arcRNA) and RNA-binding proteins. In the wild type, the blocks at the two terminal regions of arcRNAs compose the shell of paraspeckles and the middle region between the two terminal blocks composes the core, analogous to micelles of ABC triblock copolymers. We here use an extension of the theory of polymer micelles to predict the structure and size of paraspeckles as one decreases the length of one of the terminal blocks of arcRNA by CRISPR/Cas9, assuming that paraspeckles are spherical. Our theory predicts that when the length of the edited terminal blocks is larger than a critical value, paraspeckles show discontinuous transitions between the structure in which all the edited terminal blocks are localized in the shell and the structure in which all the edited terminal blocks are localized in the core at a threshold value of the transcription rate of arcRNA. In contrast, when the length of the edited terminal blocks is smaller than the critical value, the population of edited terminal blocks in the shell decreases continuously as one increases the transcription rate of arcRNA. The size of paraspeckles increases as one decreases the length of the edited terminal blocks. These predictions are consistent with our experiments.

biophysics↗