Cano, Clara

Clara is in the Gene Regulation, Epigenomics and Transcriptomics home area of the MBIDP.  She received a B.S. and an M.S. in Biochemistry from California State University, Los Angeles.  She joined the CMB training program in 2019. 

Mentor: Dr. Kathrin Plath

Research project:

      X chromosome inactivation (XCI) is the transcriptional silencing of most genes on one of the two X- chromosomes in placental female mammals, which ensures the balanced expression of sex chromosomes between XX females and XY males and is required for development and tissue homeostasis.  The X-inactive specific transcript (Xist) long non-coding RNA is the master regulator of XCI, and is induced to be expressed on one of the two X-chromosomes early in embryonic development, when the embryo implants into the uterus, or in differentiating embryonic stem cells (ESCs).  When expressed, Xist coats the future inactive X-chromosome (Xi) in cis and recruit’s several RNA-binding proteins that mediate tethering of the RNA to chromatin and gene silencing, resulting in heterochromatinization of the X-chromosome.  In humans, approximately 80 genes constitutively and 50 genes facultatively escape XCI.  XCI escapees have specific chromatin features: they carry euchromatic histone modifications, accessible chromatin, and are depleted for repressive histone marks.  Inactivated genes display an opposite pattern of chromatin features and methylated CpG islands.  A recent study from our lab suggests that Xist coats the X chromosome in a three-dimensional conformation-dependent manner, in turn modifying chromosome structure which enables the spread to newly accessible locations.  This study also demonstrated that Xist does not spread over escapees, suggesting that escape from XCI may occur because Xist is unable to spread into certain chromosomal regions.  Currently, the molecular mechanisms underlying escape from XCI are not known, beyond the finding that Xist does not cover escaping genes, nor is the complete protein interaction network of Xist known.

      My research focuses on understanding the molecular mechanisms that regulate XCI gene escape.  I will use a combination of genome editing and genomics approaches to reveal how escape is regulated.  We will use the doxycycline engineered male ESCs which are well accepted in our field to recapitulate XCI initiation.  Additionally, we will apply novel mass spectrometry approaches to understand the higher order protein network built by Xist.