title: Genome-wide identification of CBX2 targets: insights in the human sex development network.
abstract: Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role in sexual development and its disorders (disorders of sex development [DSD]), yet the exact rank and function of human CBX2 in this pathway remains unclear. Here, we performed large-scale mapping and analysis of in vivo target loci of the protein CBX2 in Sertoli-like NT-2D1 cells, using the DNA adenine methyltransferase identification technique. We identified close to 1600 direct targets for CBX2. Intriguingly, validation of selected candidate genes using qRT-PCR in cells overexpressing CBX2 or in which CBX2 has been knocked down indicated that several CBX2-responsive genes encode proteins that are involved in DSD. We further validated these effects on the candidate genes using a mutated CBX2 causing DSD in human patient. Overall, our findings suggest that CBX2 role in the sex development cascade is to stimulate the male pathway and concurrently inhibit the female pathway. These data provide fundamental insights into potential etiology of DSD.
authors.affiliation: Division of Endocrinology (W.E., A.B.-L.), Department of Medicine, University of Fribourg, 1700 Fribourg, Switzerland; and Functional Genomics Center Zurich (L.O.), University of Zurich/ETHZ, 8057 Zurich, Switzerland.
authors.forename: Wassim
authors.initials: W
authors.lastname: Eid
authors.forename: Lennart
authors.initials: L
authors.lastname: Opitz
authors.forename: Anna
authors.initials: A
authors.lastname: Biason-Lauber
mesh_terms: D002460:Cell Line; D002874:Chromosome Mapping; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D008297:Male; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D015203:Reproducibility of Results; D046468:Sexual Development / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C570479:CBX2 protein, human; D063150:Polycomb Repressive Complex 1