TY  - JOUR
TI  - Nuclear pore proteins nup153 and megator define transcriptionally active regions in the Drosophila genome.
AV  - public
SP  - e1000846 
VL  - 6
Y1  - 2010/02/12/
IS  - 2
N1  - © 2010 Vaquerizas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC2820533
N2  - Transcriptional regulation is one of the most important processes for modulating gene expression. Though much of this control is attributed to transcription factors, histones, and associated enzymes, it is increasingly apparent that the spatial organization of chromosomes within the nucleus has a profound effect on transcriptional activity. Studies in yeast indicate that the nuclear pore complex might promote transcription by recruiting chromatin to the nuclear periphery. In higher eukaryotes, however, it is not known whether such regulation has global significance. Here we establish nucleoporins as a major class of global regulators for gene expression in Drosophila melanogaster. Using chromatin-immunoprecipitation combined with microarray hybridisation, we show that Nup153 and Megator (Mtor) bind to 25% of the genome in continuous domains extending 10 kb to 500 kb. These Nucleoporin-Associated Regions (NARs) are dominated by markers for active transcription, including high RNA polymerase II occupancy and histone H4K16 acetylation. RNAi-mediated knock-down of Nup153 alters the expression of approximately 5,700 genes, with a pronounced down-regulatory effect within NARs. We find that nucleoporins play a central role in coordinating dosage compensation-an organism-wide process involving the doubling of expression of the male X chromosome. NARs are enriched on the male X chromosome and occupy 75% of this chromosome. Furthermore, Nup153-depletion abolishes the normal function of the male-specific dosage compensation complex. Finally, by extensive 3D imaging, we demonstrate that NARs contribute to gene expression control irrespective of their sub-nuclear localization. Therefore, we suggest that NAR-binding is used for chromosomal organization that enables gene expression control.
ID  - discovery1344570
UR  - http://dx.doi.org/10.1371/journal.pgen.1000846
SN  - 1553-7390
JF  - PLoS Genetics
A1  - Vaquerizas, JM
A1  - Suyama, R
A1  - Kind, J
A1  - Miura, K
A1  - Luscombe, NM
A1  - Akhtar, A
KW  - Animals
KW  -  Chromatin
KW  -  Drosophila Proteins
KW  -  Drosophila melanogaster
KW  -  Genome
KW  -  Insect
KW  -  Male
KW  -  Nuclear Matrix-Associated Proteins
KW  -  Nuclear Pore Complex Proteins
KW  -  Protein Binding
KW  -  Transcription
KW  -  Genetic
KW  -  X Chromosome
ER  -