Biology subjects

Kok, J. Y.

Publications and source records attributed to Kok, J. Y..

2 recordsLinked to original sources

bioRxiv2026

Single-residue variation in the nucleosome core reveals a regulatory hub for phenotypic innovation

Nucleosomes organize genomes and regulate DNA access, yet accumulating evidence suggests that their constituent histones may have functions beyond canonical chromatin regulation, but the breadth of such regulatory diversity remains unclear. Here, we used the six-residue loop 2 (L2) of H2A and H2A.Z to map, at single-residue resolution, how nucleosome-core variation reshapes cellular function. Genome-scale interaction mapping identified hundreds of regulatory connections spanning chromatin, as well as actin organization, endocytosis, and membrane trafficking. Interactions were residue-specific and differed between H2A and H2A.Z, revealing a regulatory landscape encoded by single residues. Transcriptome profiling showed limited expression changes and little overlap between differentially expressed genes and regulatory partners, indicating that non-chromatin connections are not readily explained by altered transcription. L2 substitutions also preferentially conferred benefits under cell wall and membrane stress. Thus, the nucleosome is linked to cellular-periphery functions beyond classical chromatin regulation, identifying histone variation as a source of phenotypic innovation.

molecular biology↗

bioRxiv2025

Nucleosome Positioning Shapes Cryptic Antisense Transcription

Maintaining transcriptional fidelity is essential for precise gene regulation and genome stability. Despite this, cryptic antisense transcription, occurring opposite to canonical coding sequences, is a pervasive feature across all domains of life. How such potentially harmful cryptic sites are regulated remains incompletely understood. Here, we show that nucleosome arrays within gene bodies play a key role in suppressing cryptic transcription. Using the fission yeast Schizosaccharomyces pombe as a model, we demonstrate that CHD1-family chromatin remodelers coordinate with the transcription elongation machinery, specifically the PAF complex, to position nucleosomes at sites of cryptic transcription initiation within gene bodies. In the absence of CHD1, AT-rich sequences within gene bodies lose nucleosome occupancy, exposing promoter-like sequences that drive cryptic initiation. While cryptic transcription is generally detrimental, we identify a subset of antisense transcripts that encode critical meiotic genes, suggesting that cryptic transcription can also serve as a source of regulatory innovation. These findings underscore the essential role of nucleosome remodelers in maintaining transcriptional fidelity and reveal their broader contributions to cellular homeostasis and evolutionary adaptability.

genetics↗