Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila

Sascha Mendjan, Mikko Taipale, Jop Kind, Herbert Holz, Philipp Gebhardt, Malgorzata Schelder, Michiel Vermeulen, Alessia Buscaino, Kent Duncan, Juerg Mueller, Matthias Wilm, Henk G. Stunnenberg, Harald Saumweber, Asifa Akhtar

Research output: Contribution to journalArticlepeer-review

330 Citations (Scopus)

Abstract

Dosage compensation in Drosophila is dependent on MSL proteins and involves hypertranscription of the male X chromosome, which ensures equal X-linked gene expression in both sexes. Here, we report the purification of enzymatically active MSL complexes from Drosophila embryos, Schneider cells, and human HeLa cells. We find a stable association of the histone H4 lysine 16-specific acetyltransferase MOF with the RNA/protein containing MSL complex as well as with an evolutionary conserved complex. We show that the MSL complex interacts with several components of the nuclear pore, in particular Mtor/TPR and Nup153. Strikingly, knockdown of Mtor or Nup153 results in loss of the typical MSL X-chromosomal staining and dosage compensation in Drosophila male cells but not in female cells. These results reveal an unexpected physical and functional connection between nuclear pore components and chromatin regulation through MSL proteins, highlighting the role of nucleoporins in gene regulation in higher eukaryotes.

Original languageEnglish
Pages (from-to)811-823
Number of pages13
JournalMolecular Cell
Volume21
Issue number6
DOIs
Publication statusPublished - 17 Mar 2006
Externally publishedYes

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