Biology subjects

Tei, S.

Publications and source records attributed to Tei, S..

3 recordsLinked to original sources

bioRxiv2025

Cohesin acts as a transcriptional gatekeeper by restraining pause-release to promote processive elongation

Cohesin organizes 3D chromatin architecture, including promoter-enhancer loops, yet its loss has surprisingly modest effects on steady-state gene expression. We address this paradox by demonstrating that cohesin acts at different stages of transcription. First, it promotes Pol II promoter recruitment by facilitating enhancer-promoter communication that maintains active promoter chromatin states. Second, it delays pause release by transiently associating with the transcriptional machinery during the pause-release transition. Kinetic modelling suggests that reduced Pol II recruitment and enhanced pause release have compensatory effects, contributing to minimal changes in steady-state gene expression across genes upon cohesin loss. In contrast, cohesin depletion impairs robust transcriptional induction in response to external stimuli. Moreover, cohesin ensures sufficient pausing duration as a quality-control-like step to promote elongation complex assembly and transcription processivity. Here, we show that cohesin regulates multiple steps of transcription, offering mechanistic insight into cohesin-related diseases, including cancers and cohesinopathies.

molecular biology↗

bioRxiv2024

Cohesin regulates promoter-proximal pausing of RNA Polymerase II by limiting recruitment of super elongation complex

Cohesin is a ring-shaped complex, responsible for establishing sister chromatid cohesion and forming topologically associating domains (TADs) and chromatin loops. Loss-of-function mutations in cohesin subunits and its regulatory factors can cause Cornelia de Lange syndrome (CdLS). Because dysregulated gene expression was observed in CdLS, it has long been thought that cohesin plays a regulatory role in transcription. Here, we investigated the effect of acute cohesin depletion on transcription and observed that a small number of genes exhibited differential expression. Analysis of RNA polymerase II (Pol II) distribution revealed that the depletion reduced Pol II promoter binding and pausing simultaneously at the majority of genes. This implies that at most genes, the two decreases counterbalance each other, resulting in unchanged gene expression. Additionally, we find that cohesin loss increased promoter binding of super elongation complex (SEC), which mediates the release of Pol II from paused state. Moreover, the reduction in pausing caused by cohesin depletion was no longer observed when SEC was inhibited. These observations suggest that cohesin regulates Pol II pausing by restricting SEC recruitment to promoters. Together, our study demonstrates the involvement of cohesin in transcriptional regulation, particularly in Pol II pause and release.

molecular biology↗

bioRxiv2020

From thoughtless awareness to effortful cognition: alpha - theta cross-frequency dynamics in experienced meditators during meditation, rest and arithmetic

Neural activity is known to oscillate within discrete frequency bands and the synchronization between these rhythms is hypothesized to underlie information integration in the brain. Since strict synchronization is only possible for harmonic frequencies, a recent theory proposes that the interaction between different brain rhythms is facilitated by transient harmonic frequency arrangements. In this line, it has been recently shown that the transient occurrence of 2:1 harmonic cross-frequency relationships between alpha and theta rhythms (i.e. falpha{approx}12 Hz; ftheta{approx}6 Hz) is enhanced during effortful cognition. In this study, we tested whether achieving a state of mental emptiness during meditation is accompanied by a relative decrease in the occurrence of 2:1 harmonic cross-frequency relationships between alpha and theta rhythms. Continuous EEG recordings (19 electrodes) were obtained from 43 highly experienced meditators during meditation practice, rest and an arithmetic task. We show that the occurrence of transient alpha:theta 2:1 harmonic relationships increased linearly from a meditative to an active cognitive processing state (i.e. meditation< rest< arithmetic task). It is argued that transient EEG cross-frequency arrangements that prevent alpha:theta cross-frequency coupling could facilitate the experience of mental emptiness by avoiding the interaction between the memory and executive components of cognition.

neuroscience↗