Diagnostic et traitement du syndrome de tachycardie orthostatique posturale

Abstract

<h3>Abstract</h3> Condensins are molecular motors that compact DNA via linear translocation. In <i>C. elegans</i>, the X-chromosome harbors a specialized condensin that participates in dosage compensation (DC). Condensin DC is recruited to and spreads from a small number of recruit elements on the X-chromosome (<i>rex</i>) and is required for the formation of topologically associating domains (TADs). We take advantage of autosomes that are largely devoid of condensin DC and TADs to address how <i>rex</i> sites and condensin DC give rise to the formation of TADs. When an autosome and X-chromosome are physically fused, despite the spreading of condensin DC into the autosome, no TAD was created. Insertion of a strong <i>rex</i> on the X-chromosome results in the TAD boundary formation regardless of sequence orientation. When the same <i>rex</i> is inserted on an autosome, despite condensin DC recruitment, there was no spreading or features of a TAD. On the other hand, when a <i>“super rex”</i> composed of six <i>rex</i> sites or three separate <i>rex</i> sites are inserted on an autosome, recruitment and spreading of condensin DC led to formation of TADs. Therefore, recruitment to and spreading from <i>rex</i> sites are necessary and sufficient for recapitulating loop-anchored TADs observed on the X-chromosome. Together our data suggest a model in which <i>rex</i> sites are both loading sites and bidirectional barriers for condensin DC, a one-sided loop-extruder with movable inactive anchor.