Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm.
Nuclear pore complexes (NPCs) mediate transport across the nuclear envelope. In yeast, they also interact with active genes, attracting or retaining them at the nuclear periphery. In higher eukaryotes, some NPC components (nucleoporins) are also found in the nucleoplasm, with a so far unknown function. We have functionally characterized nucleoporin-chromatin interactions specifically at the NPC or within the nucleoplasm in Drosophila. We analyzed genomic interactions of full-length nucleoporins Nup98, Nup50, and Nup62 and nucleoplasmic and NPC-tethered forms of Nup98. We found that nucleoporins predominantly interacted with transcriptionally active genes inside the nucleoplasm, in particular those involved in developmental regulation and the cell cycle. A smaller set of nonactive genes interacted with the NPC. Genes strongly interacting with nucleoplasmic Nup98 were downregulated upon Nup98 depletion and activated on nucleoplasmic Nup98 overexpression. Thus, nucleoporins stimulate developmental and cell-cycle gene expression away from the NPC by interacting with these genes inside the nucleoplasm.
Division of Gene Regulation, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Bernike
B
Kalverda
Helen
H
Pickersgill
Victor V
VV
Shloma
Maarten
M
Fornerod
D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D034882:Lamins / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D034882:Lamins; D028861:Nuclear Pore Complex Proteins; C547408:Nup62 protein, Drosophila; C093350:nuclear pore complex protein 98