Welcome Allana!

Allana Schooley has joined the Dekker lab team as a postdoc! Allana recently graduated at the Friedrich Miescher Laboratory of the Max Planck Society in Tuebingen, Germany under the supervision of PD Dr. Wolfram Antonin. She produced her thesis on: “The histone demethylase LSD1 regulates nuclear envelope formation at the end of Mitosis” with the support of a Max Planck fellowship.
We are very excited to have her in the lab!

 

Marlies has Graduated at University of Groningen

Marlies has graduated!

Back in Groningen, in the north of the Netherlands, Marlies Oomen has obtained her masters degree in Biology and celebrated after her graduation ceremony. Now a licensed biologist, Marlies will re-enter the Dekker lab as the newest grad student. We are excited for her return! We do however, feel a bit sorry for her, as she will once again come in to face the Worcester winter…

Marlies after graduation ceremony

Marlies (far left) after graduation ceremony

Condensin-driven remodelling of X chromosome topology during dosage compensation

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The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (∼1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using CRISPR/Cas9 greatly diminished the boundary. Thus, the DCC imposes a distinct higher-order structure onto X chromosomes while regulating gene expression chromosome-wide.

Crane, E., Bian, Q., McCord, R.P., Lajoie, B.R., Wheeler, B.S., Ralston, E.J., Uzawa, S., Dekker, J., and Meyer, B.J. (2015). Condensin-driven remodelling of X chromosome topology during dosage compensation. Nature 523, 240-244.