Recovering ensembles of chromatin conformations from contact probabilities
Open Access
- 10 November 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 41 (1), 63-75
- https://doi.org/10.1093/nar/gks1029
Abstract
The 3D higher order organization of chromatin within the nucleus of eukaryotic cells has so far remained elusive. A wealth of relevant information, however, is increasingly becoming available from chromosome conformation capture (3C) and related experimental techniques, which measure the probabilities of contact between large numbers of genomic sites in fixed cells. Such contact probabilities (CPs) can in principle be used to deduce the 3D spatial organization of chromatin. Here, we propose a computational method to recover an ensemble of chromatin conformations consistent with a set of given CPs. Compared with existing alternatives, this method does not require conversion of CPs to mean spatial distances. Instead, we estimate CPs by simulating a physically realistic, bead-chain polymer model of the 30-nm chromatin fiber. We then use an approach from adaptive filter theory to iteratively adjust the parameters of this polymer model until the estimated CPs match the given CPs. We have validated this method against reference data sets obtained from simulations of test systems with up to 45 beads and 4 loops. With additional testing against experiments and with further algorithmic refinements, our approach could become a valuable tool for researchers examining the higher order organization of chromatin.This publication has 42 references indexed in Scilit:
- The active FMR1 promoter is associated with a large domain of altered chromatin conformation with embedded local histone modificationsProceedings of the National Academy of Sciences of the United States of America, 2006
- From Silencing to Gene Expression: Real-Time Analysis in Single CellsCell, 2004
- Controlling the double helixNature, 2003
- Long-range chromatin regulatory interactions in vivoNature Genetics, 2002
- Large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoterThe Journal of cell biology, 2001
- Large-Scale Chromatin Unfolding and Remodeling Induced by VP16 Acidic Activation DomainThe Journal of cell biology, 1999
- The Organization of Replication and TranscriptionScience, 1999
- Going the Distance: A Current View of Enhancer ActionScience, 1998
- DNA LOOPINGAnnual Review of Biochemistry, 1992
- MULTIPARTITE GENETIC CONTROL ELEMENTS: COMMUNICATION BY DNA LOOPAnnual Review of Genetics, 1989