Physical mechanisms of chromatin spatial organization.
Andrea M ChiarielloSimona BiancoAndrea EspositoLuca FiorilloMattia ConteEhsan IraniFrancesco MusellaAlex AbrahamAntonella PriscoMario NicodemiPublished in: The FEBS journal (2021)
In higher eukaryotes, chromosomes have a complex three-dimensional (3D) conformation in the cell nucleus serving vital functional purposes, yet their folding principles remain poorly understood at the single-molecule level. Here, we summarize recent approaches from polymer physics to comprehend the physical mechanisms underlying chromatin architecture. In particular, we focus on two models that have been supported by recent, growing experimental evidence, the Loop Extrusion model and the Strings&Binders phase separation model. We discuss their key ingredients, how they compare to experimental data and some insight they provide on chromatin architecture and gene regulation. Progresses in that research field are opening the possibility to predict how genomic mutations alter the network of contacts between genes and their regulators and how that is linked to genetic diseases, such as congenital disorders and cancer.
Keyphrases
- single molecule
- genome wide
- transcription factor
- dna damage
- gene expression
- physical activity
- copy number
- mental health
- dna methylation
- atomic force microscopy
- living cells
- papillary thyroid
- single cell
- molecular dynamics simulations
- genome wide identification
- machine learning
- oxidative stress
- big data
- squamous cell
- mesenchymal stem cells
- artificial intelligence
- young adults
- fluorescent probe
- lymph node metastasis