| Transcriptional regulation is one of the most important processes for controlling gene expression. Until now, transcription factors and chromatin modifiers have been considered to impose much of this regulation. However, recent investigations also highlight the role of the nuclear membrane and its associated components in this process. Using chromatin-immunoprecipitation combined with high-resolution tiling arrays, we demonstrate for the first time that two components of the nuclear pore complex, Nup153 and Megator (Mtor), bind to a quarter of the Drosophila genome in continuous domains (Nucleoporin Associated Regions; NARs) spanning 10-500kb in size. NARs are typified by the presence of markers for active transcription such as high RNA polymerase II occupancy and histone H4K16 acetylation, and the absence of indicators for inactive chromatin such as H3K27me3. Immuno-FISH combined with RNAi mediated depletion revealed Nup153 dependent changes in peripheral localization of a subset of NARs. Strikingly, we reveal a link between these chromosomal regions and the dosage compensation mechanism, which doubles the expression of the male X chromosome. NARs are highly enriched on the male X chromosome compared with the rest of the autosomes, although there are no major differences for the female chromosomes. Further, NARs cover the majority of binding events of the Male Specific Lethal (MSL) complex, which is enriched on the male X chromosome. Finally, Nup153-depletion severely reduces the functionality of the MSL complex. These results firmly establish the role of nuclear pore components as a new class of genome-wide regulators for gene expression. |
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