Biology subjects

Kimura, H.

Publications and source records attributed to Kimura, H..

5 recordsLinked to original sources

bioRxiv2017

Transcription establishes microenvironments that organize euchromatin

Chromatin is organized into heterochromatin, which is transcriptionally inactive, and euchromatin, which can switch between transcriptionally active and inactive states. This switch in euchromatin activity is accompanied by changes in its spatial distribution. How euchromatin rearrangements are established is unknown. Here we use super-resolution and live-cell microscopy to show that transcriptionally inactive euchromatin moves away from transcriptionally active euchromatin. This movement is driven by the formation of RNA-enriched microenvironments that exclude inactive euchromatin. Using theory, we show that the segregation into RNA-enriched microenvironments and euchromatin domains can be considered an active microemulsion. The tethering of transcripts to chromatin via RNA polymerase II forms effective amphiphiles that intersperse the two segregated phases. Taken together with previous experiments, our data suggest that chromatin is organized in the following way: heterochromatin segregates from euchromatin by phase separation, while transcription organizes euchromatin similar to an active microemulsion.

cell biology↗

bioRxiv2017

JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states

The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Interestingly, although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed. In addition, a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and independent manner.

molecular biology↗

bioRxiv2017

NOTCH-mediated non-cell autonomous regulation of chromatinstructure during senescence

Senescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. In addition to autocrine and paracrine signalling mediated by factors of the senescence-associated secretory phenotype, we have recently identified that NOTCH1 can drive lateral induction of a unique form of senescence in adjacent cells through specific induction of the NOTCH ligand JAG1. Here we show that NOTCH signalling can modulate chromatin structure both autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) cells in culture exhibit a massive increase in nucleosome-free regions (NRFs). NOTCH signalling suppresses both SAHF and NFR formation in this context. Strikingly, NOTCH-induced senescent cells, or cancer cells with high JAG1 expression, also drive similar chromatin architectural changes in adjacent cells through cell-cell contact. Mechanistically, we show that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in a range of human cancers. Thus, HMGA1 is involved not only in SAHFs, but also RIS-specific NFR formation. In conclusion, this study identifies that the JAG1-NOTCH-HMGA1 axis mediates the juxtacrine regulation of chromatin architecture.

cell biology↗

bioRxiv2017

Effect Of Initial Body Orientation On Escape Probability In Prey Fish Escaping From Predators

Since the escape response is crucial to survival and hence to the fitness of species, several studies have attempted to elucidate the kinematic and behavioral components of the response that affect evasion outcome. The preys body orientation relative to a predator at the onset of the escape response (initial orientation) could affect evasion outcome, because the turn angle and its duration before the initiation of escape locomotion would be smaller when the initial orientation is more away from the predator. We tested this hypothesis by recording the escape responses of juvenile red sea bream (Pagrus major) in response to the predatory scorpion fish (Sebastiscus marmoratus) using a high-speed video camera. Our results show that an increased initial orientation (i.e., more away from the predator) increases escape probability. Our results also indicate that an increase in the initial orientation decreases the turn angle and its duration. The flight initiation distance tends to be small when the initial orientation is away from the predator, suggesting that the prey might have a blind zone of sensory perception. These findings highlight the importance of incorporating initial orientation into both empirical and theoretical studies of the kinematics of predator-prey interactions.\n\nSummary statementOur predator-prey experiments reveal that the preys initial body orientation relative to a predator affects the preys turn angle and its duration, and consequently affects escape probability.

animal behavior and cognition↗

bioRxiv2017

Syntaxin 17 promotes lipid droplet formation by regulating the distribution of acyl-CoA synthetase 3

Lipid droplets (LDs) are ubiquitous organelles that contain neutral lipids and are surrounded by a phospholipid monolayer. How proteins specifically localize to the phospholipid monolayer of the LD surface has been a matter of extensive investigations. Here we show that syntaxin 17 participates in LD biogenesis by regulating the distribution of acyl-CoA synthetase 3 (ACSL3), a key enzyme for LD biogenesis that redistributes from the endoplasmic reticulum to LDs during LD formation. Time course experiments revealed that syntaxin 17 binds to ACSL3 in the initial stage of LD formation, and that ACSL3 is released as a consequence of competitive binding of SNAP23 to syntaxin 17 in the maturation stage. We propose a model in which ACSL3 redistributes from the endoplasmic reticulum to LDs through association with syntaxin 17 and SNAP23-mediated dissociation from syntaxin 17. We also provide evidence that lipid raft-like structures are important for LD formation and SNAREs-ACSL3 interactions.

cell biology↗