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SUMMARY:Modeling the Genome: A view by a physicist - Jose Onuchic (Rice Un
 iversity)
DTSTART:20231213T110000Z
DTEND:20231213T120000Z
UID:TALK209449@talks.cam.ac.uk
DESCRIPTION:In vivo\, the human genome folds into a characteristic ensembl
 e of 3D structures. The mechanism driving the folding process remains unkn
 own. A theoretical model for chromatin (the minimal chromatin model) expla
 ins the folding of interphase chromosomes and generates chromosome conform
 ations consistent with experimental data is presented. The energy landscap
 e of the model was derived by using the maximum entropy principle and reli
 es on two experimentally derived inputs: a classification of loci into chr
 omatin types and a catalog of the positions of chromatin loops. This model
  was generalized by utilizing a neural network to infer these chromatin ty
 pes using epigenetic marks present at a locus\, as assayed by ChIP-Seq. Th
 e ensemble of structures resulting from these simulations completely agree
  with HI-C data and exhibits unknotted chromosomes\, phase separation of c
 hromatin types\, and a tendency for open chromatin to lie at the periphery
  of chromosome territories. Although this theoretical methodology was trai
 ned in one cell line\, the human GM12878 lymphoblastoid cells\, it has suc
 cessfully predicted the structural ensembles of multiple human cell lines.
  Finally\, going beyond Hi-C\, our predicted structures are also consisten
 t with microscopy measurements. Analysis of both structures from simulatio
 n and microscopy reveals that short segments of chromatin make two-state t
 ransitions between closed conformations and open dumbbell conformations. F
 or gene active segments\, the vast majority of genes appear clustered in t
 he linker region of the chromatin segment\, allowing us to speculate possi
 ble mechanisms by which chromatin structure and dynamics may be involved i
 n controlling gene expression.
LOCATION:Seminar Room 2\, Newton Institute
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