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PMID: 18762579 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression.

The Journal of cell biology ·Vol. 182 ·No. 5 ·2008-09-08 ·Pages 897-910

Grund SE, Fischer T, Cabal GG, Antúnez O, Pérez-Ortín JE, Hurt E

Abstract

Inner nuclear membrane proteins containing a LEM (LAP2, emerin, and MAN1) domain participate in different processes, including chromatin organization, gene expression, and nuclear envelope biogenesis. In this study, we identify a robust genetic interaction between transcription export (TREX) factors and yeast Src1, an integral inner nuclear membrane protein that is homologous to vertebrate LEM2. DNA macroarray analysis revealed that the expression of the phosphate-regulated genes PHO11, PHO12, and PHO84 is up-regulated in src1Delta cells. Notably, these PHO genes are located in subtelomeric regions of chromatin and exhibit a perinuclear location in vivo. Src1 spans the nuclear membrane twice and exposes its N and C domains with putative DNA-binding motifs to the nucleoplasm. Genome-wide chromatin immunoprecipitation-on-chip analyses indicated that Src1 is highly enriched at telomeres and subtelomeric regions of the yeast chromosomes. Our data show that the inner nuclear membrane protein Src1 functions at the interface between subtelomeric gene expression and TREX-dependent messenger RNA export through the nuclear pore complexes.

MeSH Terms
Alternative Splicing Chromatin/metabolism Chromatin Immunoprecipitation Gene Expression Regulation, Fungal Genes, Fungal Membrane Proteins/chemistry,genetics,physiology Multiprotein Complexes/physiology Nuclear Proteins/chemistry,genetics,physiology Protein Sorting Signals Protein Structure, Tertiary Proton-Phosphate Symporters/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/chemistry,genetics,physiology Telomere/genetics
Chemicals
Chromatin Membrane Proteins Multiprotein Complexes Nuclear Proteins Protein Sorting Signals Proton-Phosphate Symporters Saccharomyces cerevisiae Proteins Src1 protein, S cerevisiae
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Grund Stefanie E
Biochemie-Zentrum der Universität Heidelberg, D-69120 Heidelberg, Germany.
Fischer Tamás
Cabal Ghislain G
Antúnez Oreto
Pérez-Ortín José E
Hurt Ed
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200803098
Published
2008-09-08
Epub
2008-00-01
Pages
897-910
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2528585
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200803098 PMC Full Text View journal details
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