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: Pau Pascual-Garcia, Jieun Jeong, Maya Capelson
• Journal: Cell reports (Cell Rep) Vol. 9 Issue 2 Pg. 433-42 (Oct 23 2014) ISSN: 2211-1247 [Electronic] United States
• PMID: 25310983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromosomal Proteins, Non-Histone
• DNA-Binding Proteins
• Drosophila Proteins
• Histones
• MBD2 protein
• Nuclear Pore Complex Proteins
• nuclear pore complex protein 98
• trx protein, Drosophila

Topics

• Animals
• Chromosomal Proteins, Non-Histone (genetics, metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Drosophila (genetics, growth & development, metabolism)
• Drosophila Proteins (genetics, metabolism)
• Gene Expression Regulation, Developmental
• Genes, Homeobox
• Histones (metabolism)
• Nuclear Pore Complex Proteins (genetics, metabolism)
• Protein Binding
• Transcription, Genetic