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

• Published in: International journal of molecular sciences Vol. 25; no. 11; p. 5647
• Main Authors: Dhiman, Siddhartha, Manoj, Namya, Liput, Michal, Sangwan, Amit, Diehl, Justin, Balcerak, Anna, Sudhakar, Sneha, Augustyniak, Justyna, Jornet, Josep M, Bae, Yongho, Stachowiak, Ewa K, Dutta, Anirban, Stachowiak, Michal K
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-06-2024; MDPI
• Subjects: Analysis; Animals; Brain; Cell Differentiation - genetics; Cell division; development; entropy; Gene expression; Gene Regulatory Networks; Genes; Genome; genome integration; Genomes; Genomics; Homeostasis; Homeostasis - genetics; Humans; Metabolism; Nervous system; Neurogenesis - genetics; Neurons; Neurons - metabolism; noise and information processing; Receptor, Fibroblast Growth Factor, Type 1 - genetics; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Schizophrenia; Stem cells; System theory; Systems development; development; entropy; genome integration; schizophrenia; noise and information processing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25115647

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.