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1. Topologically associating domains and the evolution of three‐dimensional genome architecture in rice

   https://doi.org/10.1111/tpj.70139  

   Kurbidaeva, Amina; Gupta, Sonal; Zaidem, Maricris; Castanera, Raúl; Sato, Yutaka; Joly‐Lopez, Zoé; Casacuberta, Josep M; Purugganan, Michael D (May 2025, The Plant Journal)

   SUMMARY We examined the nature and evolution of three‐dimensional (3D) genome conformation, including topologically associating domains (TADs), in five genomes within the genusOryza. These included three varieties from subspecies within domesticated Asian riceO. sativaas well as their closely related wild relativesO. rufipogonandO. meridionalis. We used the high‐resolution chromosome conformation capture technique Micro‐C, which we modified for use in rice. Our analysis of rice TADs shows that TAD boundaries have high transcriptional activity, low methylation levels, low transposable element (TE) content, and increased gene density. We also find a significant correlation of expression levels for genes within TADs, suggesting that they do function as genomic domains with shared regulatory features. Our findings indicate that animal and plant TADs may share more commonalities than were initially thought, as evidenced by similar genetic and epigenetic signatures associated with TADs and boundaries. To examine 3D genome divergence, we employed a computer vision‐based algorithm for the comparison of chromatin contact maps and complemented this analysis by assessing the evolutionary conservation of individual TADs and their boundaries. We conclude that overall chromatin organization is conserved in rice, and 3D structural divergence correlates with evolutionary distance between genomes. We also note that individual TADs are not well conserved, even at short evolutionary timescales. 

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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. Expansion of a neural crest gene signature following ectopic MYCN expression in sympathoadrenal lineage cells in vivo

   https://doi.org/10.1371/journal.pone.0310727  

   Ibarra-García-Padilla, Rodrigo; Nambiar, Annika; Hamre, Thomas A; Singleton, Eileen W; Uribe, Rosa A (September 2024, PLOS ONE)

   Liu, Tao (Ed.)

   Neural crest cells (NCC) are multipotent migratory stem cells that originate from the neural tube during early vertebrate embryogenesis. NCCs give rise to a variety of cell types within the developing organism, including neurons and glia of the sympathetic nervous system. It has been suggested that failure in correct NCC differentiation leads to several diseases, including neuroblastoma (NB). During normal NCC development, MYCN is transiently expressed to promote NCC migration, and its downregulation precedes neuronal differentiation. Overexpression of MYCN has been linked to high-risk and aggressive NB progression. For this reason, understanding the effect overexpression of this oncogene has on the development of NCC-derived sympathoadrenal progenitors (SAP), which later give rise to sympathetic nerves, will help elucidate the developmental mechanisms that may prime the onset of NB. Here, we found that overexpressing human EGFP-MYCN within SAP lineage cells in zebrafish led to the transient formation of an abnormal SAP population, which displayed expanded and elevated expression of NCC markers while paradoxically also co-expressing SAP and neuronal differentiation markers. The aberrant NCC signature was corroborated within vivotime-lapse confocal imaging in zebrafish larvae, which revealed transient expansion ofsox10reporter expression in MYCN overexpressing SAPs during the early stages of SAP development. In these aberrant MYCN overexpressing SAP cells, we also found evidence of dampened BMP signaling activity, indicating that BMP signaling disruption occurs following elevated MYCN expression. Furthermore, we discovered that pharmacological inhibition of BMP signaling was sufficient to create an aberrant NCC gene signature in SAP cells, phenocopying MYCN overexpression. Together, our results suggest that MYCN overexpression in SAPs disrupts their differentiation by eliciting abnormal NCC gene expression programs, and dampening BMP signaling response, having developmental implications for the priming of NBin vivo. 

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4. The 3D architecture of the pepper genome and its relationship to function and evolution

   https://doi.org/10.1038/s41467-022-31112-x  

   Liao, Yi; Wang, Juntao; Zhu, Zhangsheng; Liu, Yuanlong; Chen, Jinfeng; Zhou, Yongfeng; Liu, Feng; Lei, Jianjun; Gaut, Brandon S.; Cao, Bihao; et al (December 2022, Nature Communications)

   Abstract The organization of chromatin into self-interacting domains is universal among eukaryotic genomes, though how and why they form varies considerably. Here we report a chromosome-scale reference genome assembly of pepper ( Capsicum annuum ) and explore its 3D organization through integrating high-resolution Hi-C maps with epigenomic, transcriptomic, and genetic variation data. Chromatin folding domains in pepper are as prominent as TADs in mammals but exhibit unique characteristics. They tend to coincide with heterochromatic regions enriched with retrotransposons and are frequently embedded in loops, which may correlate with transcription factories. Their boundaries are hotspots for chromosome rearrangements but are otherwise depleted for genetic variation. While chromatin conformation broadly affects transcription variance, it does not predict differential gene expression between tissues. Our results suggest that pepper genome organization is explained by a model of heterochromatin-driven folding promoted by transcription factories and that such spatial architecture is under structural and functional constraints. 

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5. Systems Genome: Coordinated Gene Activity Networks, Recurring Coordination Modules, and Genome Homeostasis in Developing Neurons

   https://doi.org/10.3390/ijms25115647  

   Dhiman, Siddhartha; Manoj, Namya; Liput, Michal; Sangwan, Amit; Diehl, Justin; Balcerak, Anna; Sudhakar, Sneha; Augustyniak, Justyna; Jornet, Josep M; Bae, Yongho; et al (June 2024, International Journal of Molecular Sciences)

   As human progenitor cells differentiate into neurons, the activities of many genes change; these changes are maintained within a narrow range, referred to as genome homeostasis. This process, which alters the synchronization of the entire expressed genome, is distorted in neurodevelopmental diseases such as schizophrenia. The coordinated gene activity networks formed by altering sets of genes comprise recurring coordination modules, governed by the entropy-controlling action of nuclear FGFR1, known to be associated with DNA topology. These modules can be modeled as energy-transferring circuits, revealing that genome homeostasis is maintained by reducing oscillations (noise) in gene activity while allowing gene activity changes to be transmitted across networks; this occurs more readily in neuronal committed cells than in neural progenitors. These findings advance a model of an “entangled” global genome acting as a flexible, coordinated homeostatic system that responds to developmental signals, is governed by nuclear FGFR1, and is reprogrammed in disease. 

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