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

doi:10.1016/j.molcel.2006.02.007

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

Mol Cell. 2006 Mar 17;21(6):811-23. doi: 10.1016/j.molcel.2006.02.007.

Authors

Sascha Mendjan¹, 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

Affiliation

¹ European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 169117, Heidelberg, Germany.

PMID: 16543150
DOI: 10.1016/j.molcel.2006.02.007

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetyltransferases
Animals
Animals, Genetically Modified
Cell Line
Chromatography, Affinity
Dosage Compensation, Genetic*
Drosophila / embryology
Drosophila / genetics*
Drosophila / metabolism
Drosophila Proteins / chemistry
Drosophila Proteins / metabolism*
Evolution, Molecular
Female
Gene Expression Regulation*
HeLa Cells
Humans
Male
Mass Spectrometry
Nuclear Pore / metabolism*
Nuclear Pore Complex Proteins / metabolism
Nuclear Pore Complex Proteins / physiology
Nuclear Proteins / chemistry
Nuclear Proteins / metabolism*
Protein Kinases / metabolism
Protein Kinases / physiology
TOR Serine-Threonine Kinases
Transcription Factors / chemistry
Transcription Factors / metabolism*
Transcription, Genetic*
X Chromosome / genetics

Substances

Drosophila Proteins
NUP153 protein, human
Nuclear Pore Complex Proteins
Nuclear Proteins
Transcription Factors
msl-3 protein, Drosophila
Acetyltransferases
Protein Kinases
MTOR protein, human
TOR Serine-Threonine Kinases