Biology subjects

Cerbus, R. T.

Publications and source records attributed to Cerbus, R. T..

3 recordsLinked to original sources

bioRxiv2026

Coding sequence clustering universally predicts fine- and coarse-scale chromatin compartment landscapes

Intra-chromosomal contact maps from many species display a striking plaid pattern, reflecting chromatin compartmentalization at a sub-chromosomal scale. Although widely regarded as a core feature of genome architecture, such patterns are absent in many organisms, and their underlying determinants remain unclear. Here we systematically examine the relationships among sequence features, chromatin compartmentalization, and evolutionary conservation across 247 species spanning five kingdoms. By testing the usual genomic suspects as determinants of compartmentalization within and between species, we identify the coding DNA sequence (CDS) density landscape as the most consistent predictor of compartmentalization, including whether an organism exhibits a fine-scale plaid or coarse-scale non-plaid chromatin contact map. In contrast, correlations with GC content, CpG density, or repeat element composition vary across lineages, contextualizing long-standing observations such as the prominence of chromosome G-banding in amniotes and its absence elsewhere. Notably, compartment organization is conserved across syntenic blocks between species separated by up to 1 billion years of evolution, and this conservation tracks with preservation of CDS density profiles rather than other sequence features. These findings establish the genomic distribution of coding sequences as a universal and deeply conserved organizing principle of nuclear compartment architecture.

evolutionary biology↗

bioRxiv2025

Cell cycle-resolved Hi-C reveals unexpected plasticity of A/B compartments across interphase

The spatial organization of chromatin into active (A) and inactive (B) nuclear compartments is fundamental to genome regulation, yet their cell-cycle dynamics remain largely unexplored. Most research on chromatin dynamics during the cell cycle has primarily focused on events surrounding mitosis, providing only limited insight into chromatin behavior during S-phase. To address this gap, we developed a simple, drug-free approach that combines the Fucci cell-cycle indicator with in situ Hi-C to comprehensively analyze A/B compartment dynamics throughout interphase in mouse embryonic stem cells (mESCs). Unexpectedly, and contrary to prevailing views, we found that A/B compartment strength increased abruptly upon S-phase entry, stabilized during S-phase, and subsequently declined in late S/G2. This abrupt strengthening, which we termed compartment maturation, required passage through the G1/S transition but was independent of active DNA synthesis. This maturation involved substantial architectural remodeling, particularly within the A compartment, which consolidated into a more organized structure as individual A domains rearranged to form long-range interactions. Moreover, compartment maturation was not limited to mESCs but was also evident across different developmental contexts in mice. Based on these observations, we propose a revised, stepwise model of nuclear compartmentalization during cell-cycle progression, consisting of four distinct stages: chromosome unfolding (G1), chromatin maturation (G1/S), stabilization (S phase), and refolding (G2). These findings reveal the unexpected plasticity of A/B compartments and underscore the G1/S transition as a critical period for their reorganization.

cell biology↗

bioRxiv2024

Homeotic and non-homeotic patterns in the tetrapod vertebral formula

Vertebrae can be differentiated into five categories along the body axis in tetrapods, with its numerical distribution known as the vertebral formula. The vertebral formula is a principal tool for connecting development and phylogeny [1]. This is largely due to its robust relationship with the conserved clusters of Hox genes [2], which exhibit expression boundaries coincident with vertebral divisions [3-11]. One avenue for variations in the vertebral formula is thus through Hox-mediated homeotic transformations, which manifest as a relatively fixed sum of adjacent vertebral counts. This expectation is borne out in the mammalian thoracolumbar count [12], but to date, no similar vertebral patterns have been found. Here we conduct a systematic search by generating a large dataset of complete vertebral formulae in a diverse range of tetrapod species and probing the variance of linear combinations of vertebrae. We uncover additional mammalian homeotic patterns, but also unexpected balances between distal vertebrae not comprehensible with Hox-mediated regionalization. One distal pattern appears during the progression from theropods to birds, demonstrating its phylogenetic importance. We further show that several vertebral counts correlate with posterior intergenic distances in the HoxB gene cluster. By creating a vertebral formula database and mathematically defining patterns, our work establishes a quantitative approach for comparative genomics in morphology.

evolutionary biology↗