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1. Global Genome Conformational Programming during Neuronal Development Is Associated with CTCF and Nuclear FGFR1—The Genome Archipelago Model

   https://doi.org/10.3390/ijms22010347  

   Decker, Brandon; Liput, Michal; Abdellatif, Hussam; Yergeau, Donald; Bae, Yongho; Jornet, Josep M.; Stachowiak, Ewa K.; Stachowiak, Michal K. (January 2021, International Journal of Molecular Sciences)

   null (Ed.)

   During the development of mouse embryonic stem cells (ESC) to neuronal committed cells (NCC), coordinated changes in the expression of 2851 genes take place, mediated by the nuclear form of FGFR1. In this paper, widespread differences are demonstrated in the ESC and NCC inter- and intra-chromosomal interactions, chromatin looping, the formation of CTCF- and nFGFR1-linked Topologically Associating Domains (TADs) on a genome-wide scale and in exemplary HoxA-D loci. The analysis centered on HoxA cluster shows that blocking FGFR1 disrupts the loop formation. FGFR1 binding and genome locales are predictive of the genome interactions; likewise, chromatin interactions along with nFGFR1 binding are predictive of the genome function and correlate with genome regulatory attributes and gene expression. This study advances a topologically integrated genome archipelago model that undergoes structural transformations through the formation of nFGFR1-associated TADs. The makeover of the TAD islands serves to recruit distinct ontogenic programs during the development of the ESC to NCC. 

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2. Systems genome, Gene Activity Networks, and Recurrent Activity Motifs in control of genome homeostasis; a role of nuclear FGFR1

   J. Diehl, N. Manoj (January 2022, 8th Genetics, Genomics, and Bioinformatics Annual Research Day at the University at Buffalo)

   During transition of human Neural Progenitor Cells (NPC) to Neuronal Committed Cells (NCC) activities of 4706 genes change their activities. These changes obey the Gaussian principle whereby the majority are moderate and few represent extreme up- or down-regulations. Inhibition of pan-ontogenic nuclear Fibroblast Growth Factor Receptor 1 (nFGFR1) signaling, which mediates the NPC to NCC differentiation, affected the activities of hundreds of genes in NPC and in NCC. Our new results show that nFGFR1 acts as a Band-Path filter that maintains global genome function within a homeostatic range by diminishing extreme changes and promoting moderate changes. To elaborate on the underlying mechanism, we analyzed Pearson correlation among the genes of the regulated genome. The majority of 4007 gene activities were highly coordinated and their frequencies were increased during the NPC to NCC transition while the low coordinated genes were decreased. The frequencies of high and low coordinated genes were affected by the inhibition of endogenous nFGFR1 and by the overexpression of constitutively active nFGFR1. Analysis of Gene Activity Networks (GANs) formed by the most coordinated neurodevelopmental genes showed that NPC to NCC transition is accompanied by a deconstruction of NPC GANs and construction of new NCC GANs and that the formation of GANs is largely dependent on the endogenous levels of nFGFR1. Within the GANs we identified several overrepresented Recurring Correlation Motifs (RCM) which undergo frequency redistribution during differentiation. The high complexity motifs (with a high number of connections) increased during GANs’ construction and decreased during GANs’ deconstruction. The ability of the RCM to counteract excessive gene activity oscillation during differentiation was analyzed by modelling their function as electrical RLC equivalent networks with genes serving as inductors (L) and the equivalent Spring-mass oscillator model. In RLC circuits, where the reduced inductance value from star network arrangement dampens the oscillations, increased motifs complexity dampens down the oscillations in the individual nodes (genes) activities as the network transits between different activity levels. In conclusion, deselection of low complexity of motifs and selection of more complex motifs by nFGFR1 serve to maintain the genome homeostasis during development. A Proportional–Integral–Derivative (PID) controller model with the RLC lumped element equivalents is proposed employing nFGFR1 feedback as a control system of the ontogenic gene programs. 

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3. Genome-wide signatures of plastid-nuclear coevolution point to repeated perturbations of plastid proteostasis systems across angiosperms

   https://doi.org/10.1093/plcell/koab021  

   Forsythe, Evan S; Williams, Alissa M; Sloan, Daniel B (January 2021, The Plant Cell)

   null (Ed.)

   Abstract Nuclear and plastid (chloroplast) genomes experience different mutation rates, levels of selection, and transmission modes, yet key cellular functions depend on their coordinated interactions. Functionally related proteins often show correlated changes in rates of sequence evolution across a phylogeny (evolutionary rate covariation or ERC), offering a means to detect previously unidentified suites of coevolving and cofunctional genes. We performed phylogenomic analyses across angiosperm diversity, scanning the nuclear genome for genes that exhibit ERC with plastid genes. As expected, the strongest hits were highly enriched for genes encoding plastid-targeted proteins, providing evidence that cytonuclear interactions affect rates of molecular evolution at genome-wide scales. Many identified nuclear genes functioned in post-transcriptional regulation and the maintenance of protein homeostasis (proteostasis), including protein translation (in both the plastid and cytosol), import, quality control and turnover. We also identified nuclear genes that exhibit strong signatures of coevolution with the plastid genome, but their encoded proteins lack organellar-targeting annotations, making them candidates for having previously undescribed roles in plastids. In sum, our genome-wide analyses reveal that plastid-nuclear coevolution extends beyond the intimate molecular interactions within chloroplast enzyme complexes and may be driven by frequent rewiring of the machinery responsible for maintenance of plastid proteostasis in angiosperms. 

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4. Fluctuation structure predicts genome-wide perturbation outcomes

   https://doi.org/10.1101/2025.06.27.661814  

   Kuznets-Speck, Benjamin; Schwartz, Leon; Sun, Hanxiao; Melzer, Madeline E; Kumari, Nitu; Haley, Benjamin; Prashnani, Ekta; Vaikuntanathan, Suriyanarayanan; Goyal, Yogesh (July 2025, bioRxiv)

   Pooled single-cell perturbation screens represent powerful experimental platforms for functional genomics, yet interpreting these rich datasets for meaningful biological conclusions remains challenging. Most current methods fall at one of two extremes: either opaque deep learning models that obscure biological meaning, or simplified frameworks that treat genes as isolated units. As such, these approaches overlook a crucial insight: gene co-fluctuations in unperturbed cellular states can be harnessed to model perturbation responses. Here we present CIPHER (Covariance Inference for Perturbation and High-dimensional Expression Response), a framework leveraging linear response theory from statistical physics to predict transcriptome-wide perturbation outcomes using gene co-fluctuations in unperturbed cells. We validated CIPHER on synthetic regulatory networks before applying it to 11 large-scale single-cell perturbation datasets covering 4,234 perturbations and over 1.36M cells. CIPHER robustly recapitulated genome-wide responses to single and double perturbations by exploiting baseline gene covariance structure. Importantly, eliminating gene-gene covariances, while retaining gene-intrinsic variances, reduced model performance by 11-fold, demonstrating the rich information stored within baseline fluctuation structures. Moreover, gene-gene correlations transferred successfully across independent experiments of the same cell type, revealing stereotypic fluctuation structures. Furthermore, CIPHER outperformed conventional differential expression metrics in identifying true perturbations while providing uncertainty-aware effect size estimates through Bayesian inference. Finally, most genome-wide responses propagated through the covariance matrix along approximately three independent and global gene modules. CIPHER underscores the importance of theoretically-grounded models in capturing complex biological responses, highlighting fundamental design principles encoded in cellular fluctuation patterns. 

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5. High‐quality chromosome‐level genome assembly and multi‐omics analysis of rosemary ( Salvia rosmarinus ) reveals new insights into the environmental and genome adaptation

   https://doi.org/10.1111/pbi.14305  

   Lai, Yong; Ma, Jinghua; Zhang, Xuebin; Xuan, Xiaobo; Zhu, Fengyun; Ding, Shen; Shang, Fude; Chen, Yuanyuan; Zhao, Bing; Lan, Chen; et al (July 2024, Plant Biotechnology Journal)

   Summary High‐quality genome of rosemary (Salvia rosmarinus) represents a valuable resource and tool for understanding genome evolution and environmental adaptation as well as its genetic improvement. However, the existing rosemary genome did not provide insights into the relationship between antioxidant components and environmental adaptability. In this study, by employing Nanopore sequencing and Hi‐C technologies, a total of 1.17 Gb (97.96%) genome sequences were mapped to 12 chromosomes with 46 121 protein‐coding genes and 1265 non‐coding RNA genes. Comparative genome analysis reveals that rosemary had a closely genetic relationship withSalvia splendensandSalvia miltiorrhiza, and it diverged from them approximately 33.7 million years ago (MYA), and one whole‐genome duplication occurred around 28.3 MYA in rosemary genome. Among all identified rosemary genes, 1918 gene families were expanded, 35 of which are involved in the biosynthesis of antioxidant components. These expanded gene families enhance the ability of rosemary adaptation to adverse environments. Multi‐omics (integrated transcriptome and metabolome) analysis showed the tissue‐specific distribution of antioxidant components related to environmental adaptation. During the drought, heat and salt stress treatments, 36 genes in the biosynthesis pathways of carnosic acid, rosmarinic acid and flavonoids were up‐regulated, illustrating the important role of these antioxidant components in responding to abiotic stresses by adjusting ROS homeostasis. Moreover, cooperating with the photosynthesis, substance and energy metabolism, protein and ion balance, the collaborative system maintained cell stability and improved the ability of rosemary against harsh environment. This study provides a genomic data platform for gene discovery and precision breeding in rosemary. Our results also provide new insights into the adaptive evolution of rosemary and the contribution of antioxidant components in resistance to harsh environments. 

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