Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila.
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.
European Molecular Biology Laboratory, Gene Expression Programme, Meyerhofstrasse 169117, Heidelberg, Germany.
Sascha
S
Mendjan
Mikko
M
Taipale
Jop
J
Kind
Herbert
H
Holz
Philipp
P
Gebhardt
Malgorzata
M
Schelder
Michiel
M
Vermeulen
Alessia
A
Buscaino
Kent
K
Duncan
Juerg
J
Mueller
Matthias
M
Wilm
Henk G
HG
Stunnenberg
Harald
H
Saumweber
Asifa
A
Akhtar
D000123:Acetyltransferases; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D002846:Chromatography, Affinity; D004303:Dosage Compensation, Genetic; D004330:Drosophila / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism / Q000502:physiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D014960:X Chromosome / Q000235:genetics
D029721:Drosophila Proteins; C079377:NUP153 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C093904:msl-3 protein, Drosophila; D000123:Acetyltransferases; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases