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Seeber, A.

Publications and source records attributed to Seeber, A..

2 recordsLinked to original sources

Single particle trajectory statistic to reconstruct chromatin organization and dynamics

Chromatin organization remains complex and far from understood. We discuss here recent statistical methods to extract biophysical parameters from in vivo single particle trajectories of loci to reconstruct chromatin reorganization in response to cellular stress such as DNA damages. We look at the methods to analyze both single loci as well as multiple loci tracked simultaneously and explain how to quantify and describe chromatin motion using a combination of extractable parameters. These parameters can be converted into information about chromatin dynamics and function. Furthermore, we discuss how the time scale of recurrent motion of a locus can be extracted and converted into local chromatin dynamics. We also discuss the effect of various sampling rates on the estimated parameters. Finally, we discuss polymer methods based on cross-linkers that account for minimal loop constraints hidden in tracked loci, that reveal chromatin organization at the 250nm spatial scale. We list and refer to some algorithm packages that are now publicly available. To conclude, chromatin organization and dynamics at hundreds of nanometers can be reconstructed from locus trajectories and predicted based on polymer models.

genomics

Local decondensation at double-stranded DNA breaks modifies chromatin at long distances and reduces encounter times during homology search

Double-strand break (DSB) repair by homologous recombination (HR) requires an efficient and timely search for a homologous template. Here we first study global chromatin re-organization following a single DSB: due to the potential release of cross-linkers such as cohesin and CTCF molecules near the DSB site, loops are released and chromatin is decondensed, explaining the change of chromatin locus motion at larger genomic distances. This mechanism provides an elementary explanation for the increase of the anomalous exponent at sites located far away from the DSB, after break induction. Second, we explore the consequences of chromatin reorganization for the homology search during DNA repair: using polymer models, we estimate the mean first encounter time (MFET) between two loci on the chromatin in a confined nucleus. Reducing tethering forces, as reported experimentally on chromatin, is associated with a local de-condensation near the break followed by the extrusion of the breaks. Consequently, we report here that the mean first encounter time between homologous sites is decreased by two orders of magnitude even when the homologue sequence is located on the nuclear boundary. To conclude, our results suggest that local changes in inter-nucleosomal contacts near DSBs, by cohesin removal, remodel the chromatin and drastically shorten the time required to complete a long-range search for a homologous template.

genetics