title: Evolutionary diversification of SPANX-N sperm protein gene structure and expression.
abstract: The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage approximately 7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well.
authors.affiliation: Laboratory of Molecular Pharmacology, National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, United States of America. kouprinn@mail.nih.gov
authors.forename: Natalay
authors.initials: N
authors.lastname: Kouprina
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Noskov
authors.forename: Adam
authors.initials: A
authors.lastname: Pavlicek
authors.forename: N Keith
authors.initials: NK
authors.lastname: Collins
authors.forename: Pamela D
authors.initials: PD
authors.lastname: Schoppee Bortz
authors.forename: Chris
authors.initials: C
authors.lastname: Ottolenghi
authors.forename: Dmitri
authors.initials: D
authors.lastname: Loukinov
authors.forename: Paul
authors.initials: P
authors.lastname: Goldsmith
authors.forename: John I
authors.initials: JI
authors.lastname: Risinger
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: V Anne
authors.initials: VA
authors.lastname: Westbrook
authors.forename: Gregory
authors.initials: G
authors.lastname: Solomon
authors.forename: Hanna
authors.initials: H
authors.lastname: Sounders
authors.forename: John C
authors.initials: JC
authors.lastname: Herr
authors.forename: Jerzy
authors.initials: J
authors.lastname: Jurka
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Vladimir
authors.initials: V
authors.lastname: Larionov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X; D024202:Electrophoretic Mobility Shift Assay; D019143:Evolution, Molecular; D005455:Fluorescent Antibody Technique; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000276:immunology; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D009687:Nuclear Proteins; D011994:Recombinant Proteins; C414403:SPANXA1 protein, human