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

Area of Science:

• Neuroscience
• Genetics
• Systems Biology

Background:

• During neuronal differentiation, gene activity is maintained within a narrow range, a process termed genome homeostasis.
• This genome homeostasis is disrupted in neurodevelopmental diseases like schizophrenia.
• Coordinated gene activity networks form recurring modules regulated by nuclear FGFR1, which influences DNA topology.

Purpose of the Study:

• To investigate the mechanisms underlying genome homeostasis during neuronal differentiation.
• To explore the role of nuclear FGFR1 in regulating gene activity networks.
• To model genome homeostasis as an energy-transferring circuit and understand its disruption in disease.

Main Methods:

• Modeling coordinated gene activity networks as energy-transferring circuits.
• Analyzing the role of nuclear FGFR1 in controlling gene activity oscillations (noise).
• Comparing gene activity transmission in neuronal progenitors versus committed neuronal cells.

Main Results:

• Genome homeostasis is maintained by reducing gene activity noise and facilitating signal transmission across networks.
• This process is more efficient in neuronal committed cells than in neural progenitors.
• Nuclear FGFR1 acts as an entropy-controlling factor in these gene activity networks.

Conclusions:

• Genome homeostasis represents a flexible, coordinated system governed by nuclear FGFR1 and responsive to developmental signals.
• Disruptions in this homeostatic system, particularly in FGFR1 regulation, are implicated in neurodevelopmental diseases.
• A model of an "entangled" global genome is proposed, highlighting its dynamic and responsive nature.