Differentially regulated and evolved genes in the fully sequenced Xq/Yq pseudoautosomal region

Abstract

Human sex chromosomes, which are morphologically and genetically different, share few regions of homology. Among them, only pseudoautosomal regions (PARs) pair and recombine during meiosis. To better address the complex biology of these regions, we sequenced the telomeric 400 kb of the long arm of the human X chromosome, including 330 kb of the human Xq/YqPAR and the telomere. Sequencing reveals subregions with distinctive regulatory and evolutionary features. The proximal 295 kb contains two genes inactivated on both the inactive X and Y chromosomes [ SYBL1 and a novel homologue ( HSPRY3 ) of Drosophila sprouty ]. The GC-rich distal 35 kb, added in stages and much later in evolution, contains the X/Y expressed gene IL9R and a novel gene, CXYorf1, only 5 kb from the Xq telomere. These properties make Xq/YqPAR a model for studies of region-specific gene inactivation, telomere evolution, and involvement in sex-limited conditions.

FGF signaling inhibitor, SPRY4, is evolutionarily conserved target of WNT signaling pathway in progenitor cells

“…SPROUTY (SPRY) and SPRED family genes encode inhibitors for receptor tyrosine kinase signaling cascades, such as those of FGF receptor family members and EGF receptor family members (29)(30)(31)(32)(33)(34)(35). Here, transcriptional regulation of SPRY1, SPRY2, SPRY3, SPRY4, SPRED1, SPRED2, and SPRED3 genes by WNT/ß-catenin signaling pathway was investigated by using bioinformatics and human intelligence.…”

“…Hedgehog signals are transduced through Patched receptors and Smoothened signal transducers to activate transcription of target genes, such as PTCH1, SFRP1, CCND2 and FOXM1 genes, based on active form of GLI family transcription factors (6-9,25-28). WNT, FGF, and Hedgehog signaling pathways network together during embryogenesis, tissue regeneration, and carcinogenesis.SPROUTY (SPRY) and SPRED family genes encode inhibitors for receptor tyrosine kinase signaling cascades, such as those of FGF receptor family members and EGF receptor family members (29)(30)(31)(32)(33)(34)(35). Here, transcriptional regulation of SPRY1, SPRY2, SPRY3, SPRY4, SPRED1, SPRED2, and SPRED3 genes by WNT/ß-catenin signaling pathway was investigated by using bioinformatics and human intelligence.…”

Complex Events in the Evolution of the Human Pseudoautosomal Region 2 (PAR2)

“…HSPRY3 and SYBL1 are both inactive on the Y and are subject to X inactivation in humans. In contrast, IL9R and CXYorf1 are expressed from the Y and are not subject to X inactivation (Huber et al 1999;Ciccodicola et al 2000).…”

“…Recently, the entire human PAR2 was sequenced and found to contain two other genes HSPRY3 (homolog to Drosophila sprouty 3) and CXYorf1, as well as a number of fragmentary pseudogenes (Ciccodicola et al 2000). The order of the genes from centromere to telomere is HSPRY3, SYBL1, IL9R, and CXYorf1.…”

“…HSPRY3 and SYBL1 both map to the X, but not the Y, in primate and the mouse. IL9R maps to the X in primate but is autosomal in mouse (Kermouni et al 1995;D'Esposito et al 1997;Vermeesch et al 1997;Matarazzo et al 1999;Ciccodicola et al 2000) (Table 1). HSPRY3 and SYBL1 are both inactive on the Y and are subject to X inactivation in humans.…”