Biology subjects

Hungyo, K.

Publications and source records attributed to Hungyo, K..

3 recordsLinked to original sources

bioRxiv2026

Histone H2BK108Me2 Tunes Gluconeogenic Load in Type 2 Diabetes: A Molecular Dynamics Study

Type 2 Diabetes (T2D) is a serious metabolic disorder characterised by hyperglycemia, hyperinsulinemia, and insulin resistance. An increased rate of hepatic gluconeogenesis acts as one of the major contributors of the high blood glucose levels in the diseased condition. Transcriptional regulation is a main factor that controls gene expression. In this study we have investigated how the transcriptional availability of the Cebpa gene can be modulated at the nucleosomal level through the post-translational modifications (PTMs) of histones using a series of coarse-grained multi-microsecond molecular dynamics (MD) simulations. Our work explores the structural modulations imposed by histone PTMs on the Cebpa +1 nucleosome in terms of histone-DNA interactions, nucleosome unwrapping, and nucleosome sliding, which can further contribute to the alteration in transcription of the gene. The MD simulations reveal that the histone mark H2BK108Me2--a downregulated histone PTM mark found in a diet-induced obese mouse liver--can steer the nucleosome sliding in a direction such that the transcription start site of Cebpa gene tends to close. This study predicts H2BK108Me2 to be a potential histone PTM mark which might be involved in tackling gluconeogenic load by closure of nucleosomal DNA ends of Cebpa +1 nucleosome via sliding and posing chromatin unavailability towards essential transcription factors of the gene. Author SummaryHistone PTMs regulate transcription of genes by altering nucleosome dynamics, yet, their precise mechanisms and effects remain unclear. Here, microsecond time-scale MD simulations with SIRAH forcefield reveals how T2D associated PTMs change DNA accessibility and reshape nucleosome conformation on the +1 nucleosome of a gluconeogenic regulator gene Cebpa. Our analysis uncovers changes in histone-DNA interactions, DNA trajectories, and nucleosome sliding to be the probable mechanisms of altered transcriptional output. This work attempts to bridge the gap between structural effects of nucleosomes and disease biology by providing a mechanistic link between metabolic disease epigenetics and chromatin biophysics. It demonstrates the role of PTMs in modulating the gene expression through collective nucleosome motions and offering insights into therapeutic targeting of histone PTMs.

biophysics↗

bioRxiv2025

CpG-induced regions associated compositional stratification of human essential proteins through mathematical genomics

CpG islands are genomic regions enriched in cytosine-phosphate-guanine dinucleotides, typically associated with gene promoters and regulatory elements. While their role in transcriptional regulation is well established, their influence on protein sequence composition remains underexplored. In this study, 3,222 essential proteins from Homo sapiens were analyzed to investigate the impact of CpG island architecture on amino acid usage, sequence complexity, and chromosomal distribution. Codons containing both cytosine and guanine were mapped to five CpG-induced amino acids, and their relative abundance was quantified across proteins. CpG-induced regions were identified using a sliding window approach, and metrics such as average CpG density, longest CpG-induced region length, and sequence coverage were computed. Motif composition within these regions was characterized using polarity and charge-based indices. Clustering revealed consistent bipartite subgroup structures, indicating compositional stratification among essential proteins. Shannon entropy quantified compositional complexity, revealing a significant shift between clusters (p = 5. x 50 10-145). Cluster 1 proteins showed lower entropy and greater heterogeneity, whereas Cluster 2 showed higher entropy and tighter distributions, indicating distinct regimes of variability. Additionally, we examined CpG island overlap within coding exons of essential genes and found that CpG-depleted proteins are predominantly encoded by genes with minimal CGI coverage, whereas CpG-induced proteins span both low- and high-overlap classes. CGI-associated CpGs were consistently enriched toward the 5' end of essential genes, indicating a positional bias in CpG distribution. These findings establish a quantitative framework linking CpG island distribution to proteomic architecture and offer a scalable strategy for motif annotation, epigenetic modeling, and functional stratification. Future applications include predictive modeling of protein function, disease association, and regulatory dynamics.

genomics↗

bioRxiv2023

Decoding Nucleosome-Depleted Regions: Insights from Epigenetic Marks, Nucleosome Size, and Thermodynamic Modelling

Elucidating the global and local rules that govern genome-wide nucleosome organisation and chromatin architecture remains a critical challenge. Thermodynamic modelling based on DNA elastic properties predicts the presence of sequence-encoded nucleosome-inhibiting energy barriers (NIEBs) along vertebrate genomes. They delineate in vivo nucleosome-depleted regions (NDRs) flanked by 2-3 well positioned nucleosomes. Here, we compared mouse NIEBs to NDRs observed at CTCF binding sites and active TSSs to reveal specific chromatin organizations. We uncover in MNase-seq chromatin profiles the presence of particles of subnucleosomal length specifically positioned at the border of NIEBs with an enrichment of H3.3 and its modification H3.3 S31Ph, whereas the positioning of nucleosomes bearing H3K27ac appears insensitive to NIEBs. Surprisingly, post-translational modifications affect the size distribution of nucleosomes as seen by MNase digestion and so likely their breathing capability. We implemented an extension of our thermodynamic model allowing for variable particle size and suggest that subnucleomes at NIEB borders would result from the recruitment of chromatin remodellers at NIEBs. Our findings provide new insights into the mechanisms by which the DNA sequence and epigenetic marks shape the nucleosome positioning and breathing.

genomics↗