title: Nucleoporin Nup98 associates with Trx/MLL and NSL histone-modifying complexes and regulates Hox gene expression.
abstract: The nuclear pore complex is a transport channel embedded in the nuclear envelope and made up of 30 different components termed nucleoporins (Nups). In addition to their classical role in transport, a subset of Nups has a conserved role in the regulation of transcription via direct binding to chromatin. The molecular details of this function remain obscure, and it is unknown how metazoan Nups are recruited to their chromatin locations or what transcription steps they regulate. Here, we demonstrate genome-wide and physical association between Nup98 and histone-modifying complexes MBD-R2/NSL [corrected] and Trx/MLL. Importantly, we identify a requirement for MBD-R2 in recruitment of Nup98 to many of its genomic target sites. Consistent with its interaction with the Trx/MLL complex, Nup98 is shown to be necessary for Hox gene expression in developing fly tissues. These findings introduce roles of Nup98 in epigenetic regulation that may underlie the basis of oncogenicity of Nup98 fusions in leukemia.
authors.affiliation: Department of Cell and Developmental Biology, Penn Epigenetics Program, University of Pennsylvania, 9-101 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Pau
authors.initials: P
authors.lastname: Pascual-Garcia
authors.affiliation: Department of Cell and Developmental Biology, Penn Epigenetics Program, University of Pennsylvania, 9-101 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Jieun
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Cell and Developmental Biology, Penn Epigenetics Program, University of Pennsylvania, 9-101 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address: capelson@mail.med.upenn.edu.
authors.forename: Maya
authors.initials: M
authors.lastname: Capelson
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D006657:Histones / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; C115368:MBD2 protein; D028861:Nuclear Pore Complex Proteins; C093350:nuclear pore complex protein 98; C512571:trx protein, Drosophila