Modeling the Genome: A view by a physicist

Add to your list(s) Download to your calendar using vCal

• Jose Onuchic (Rice University)
• Wednesday 13 December 2023, 11:00-12:00
• Seminar Room 2, Newton Institute.

If you have a question about this talk, please contact nobody.

SPL - New statistical physics in living matter: non equilibrium states under adaptive control

In vivo, the human genome folds into a characteristic ensemble of 3D structures. The mechanism driving the folding process remains unknown. A theoretical model for chromatin (the minimal chromatin model) explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data is presented. The energy landscape of the model was derived by using the maximum entropy principle and relies on two experimentally derived inputs: a classification of loci into chromatin types and a catalog of the positions of chromatin loops. This model was generalized by utilizing a neural network to infer these chromatin types using epigenetic marks present at a locus, as assayed by ChIP-Seq. The ensemble of structures resulting from these simulations completely agree with HI-C data and exhibits unknotted chromosomes, phase separation of chromatin types, and a tendency for open chromatin to lie at the periphery of chromosome territories. Although this theoretical methodology was trained in one cell line, the human GM12878 lymphoblastoid cells, it has successfully predicted the structural ensembles of multiple human cell lines. Finally, going beyond Hi-C, our predicted structures are also consistent with microscopy measurements. Analysis of both structures from simulation and microscopy reveals that short segments of chromatin make two-state transitions between closed conformations and open dumbbell conformations. For gene active segments, the vast majority of genes appear clustered in the linker region of the chromatin segment, allowing us to speculate possible mechanisms by which chromatin structure and dynamics may be involved in controlling gene expression.

This talk is part of the Isaac Newton Institute Seminar Series series.

This talk is included in these lists:

• All CMS events
• Featured lists
• INI info aggregator
• Isaac Newton Institute Seminar Series
• School of Physical Sciences
• Seminar Room 2, Newton Institute
• bld31

Note that ex-directory lists are not shown.