Biology subjects

Tanegashima, C.

Publications and source records attributed to Tanegashima, C..

4 recordsLinked to original sources

bioRxiv2024

Engineered acetylation patterns drive large-scale chromatin organization in vitro

Chromatin organization plays a crucial role in gene regulation [1, 2, 3], but disentangling the contributions of various epigenetic components to gene-scale chromatin structure remains challenging. While in vitro chromatin reconstitution enables controlled studies on the effect of bio-chemical factors on the structure, current methods are either limited to short arrays or lack control over histone modification patterns. Here we directly test how histone modification affects higher-order chromatin architecture by characterizing gene-scale reconstituted chromatin using single-molecule microscopy and in vitro Hi-C. We reconstitute 20-kilobase chromatin arrays with histone modification patterns controlled at 12-nucleosome resolution, achieving complete assembly of 96 nucleosomes in the designed order as confirmed by atomic force microscopy and longread sequencing. Observing end-to-end fluctuations of the reconstituted arrays, we find that increasing the density of acetylated nucleosomes leads to larger structural fluctuations with longer relaxation times, consistent with the predictions of a polymer model with hydrodynamic interactions. We demonstrate through in vitro Hi-C how acetylation reduces contact frequency between nucleosomes and induces open conformations. In heterogeneously modified arrays, differential contact probabilities between acetylated and unmodified regions lead to distinct structural domains. The results establish the physical principles by which histone modifications directly modulate chromatin architecture through altered nucleosome-nucleosome interactions, providing a quantitative framework for understanding and engineering genome organization.

biophysics↗

bioRxiv2021

Single-cell transcriptome atlas of Drosophila gastrula 2.0

During development, positional information directs cells to specific fates, leading them to differentiate with their own transcriptomes and express specific behaviors and functions. However, the mechanisms underlying these processes in a genome-wide view remain ambiguous, partly because the single-cell transcriptomic data of early developing embryos containing both accurate spatial and lineage information is still lacking. Here, we report a new single-cell transcriptome atlas of Drosophila gastrulae, divided into 65 transcriptomically distinct clusters. We found that the expression profiles of plasma-membrane-related genes, but not those of transcription factor genes, represented each germ layer, supporting the nonequivalent contribution of each transcription factor mRNA level to effector gene expression profiles at the transcriptome level. We also reconstructed the spatial expression patterns of all genes at the single-cell stripe level as the smallest unit. This atlas is an important resource for the genome-wide understanding of the mechanisms by which genes cooperatively orchestrate Drosophila gastrulation.

developmental biology↗

bioRxiv2020

Developmental hourglass and heterochronic shifts in fin and limb development

How genetic changes are linked to morphological novelties and developmental constraints remains elusive. Here we investigate genetic apparatuses that distinguish fish fins from tetrapod limbs by analyzing transcriptomes and open chromatin regions (OCRs). Specifically, we compare mouse forelimb buds with pectoral fin buds of a slowly evolving species, the brown-banded bamboo shark (Chiloscyllium punctatum). A transcriptomic comparison with an accurate orthology map reveals both a mass heterochrony and hourglass-shaped conservation of gene expression between fins and limbs. Furthermore, chromatin-accessibility data indicate that conserved regulatory sequences are most active during mid-stage limb development. During this stage, stage-specific and tissue-specific OCRs are also enriched. Together, early and late stages of fin/limb development are more permissive to mutations, which may have contributed to the major morphological changes during the fin-to-limb evolution. We also hypothesize that the middle stages are constrained by regulatory complexity that results from dynamic and tissue-specific transcriptional controls.

evolutionary biology↗

bioRxiv2018

Hair Follicle Epidermal Stem Cells Define a Niche for Tactile Sensation

The heterogeneity and compartmentalization of stem cells is a common principle in many epithelia, and is known to function in epithelial maintenance, but its other physiological roles remain elusive. Here we show transcriptional and anatomical contributions of compartmentalized epidermal stem cells (EpSCs) in tactile sensory unit formation in the hair follicle (HF). EpSCs in the follicle upper-bulge, where mechanosensory lanceolate complexes (LCs) innervate, express a unique set of extracellular matrix (ECM) and neurogenesis-related genes. These EpSCs deposit an ECM protein EGFL6 into the collar matrix, a novel ECM that tightly ensheathes LCs. EGFL6 is required for the proper patterning, touch responses, and v integrin-enrichment of LCs. By maintaining a quiescent original EpSC niche, the old bulge, EpSCs provide anatomically stable HF-LC interfaces, irrespective of the stage of follicle regeneration cycle. Thus, compartmentalized EpSCs provide a niche linking the HF and the nervous system throughout the hair cycle.

developmental biology↗