Sensing X Chromosome Pairs Before X Inactivation via a Novel X-Pairing Region of the Xic

Abstract

Mammalian dosage compensation involves silencing of one of the two X chromosomes in females and is controlled by the X-inactivation center ( Xic ). The Xic , which includes Xist and its antisense transcription unit Tsix/Xite , somehow senses the number of X chromosomes and triggers Xist up-regulation from one of the two X chromosomes in females. We found that a segment of the mouse Xic lying several hundred kilobases upstream of Xist brings the two Xic s together before the onset of X inactivation. This region can autonomously drive Xic trans-interactions even as an ectopic single-copy transgene. Its introduction into male embryonic stem cells is strongly selected against, consistent with a possible role in trans-activating Xist . We propose that homologous associations driven by this novel X-pairing region ( Xpr ) of the Xic enable a cell to sense that more than one X chromosome is present and coordinate reciprocal Xist/Tsix expression.