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Published online September 1, 2008
doi:10.1083/jcb.200803098
The Journal of Cell Biology, Vol. 182, No. 5, 897-910
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Grund et al.
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Article

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

Stefanie E. Grund1, Tamás Fischer1, Ghislain G. Cabal2, Oreto Antúnez3,4, José E. Pérez-Ortín3,4, and Ed Hurt1

1 Biochemie-Zentrum der Universität Heidelberg, D-69120 Heidelberg, Germany
2 Unité de Biologie Cellulaire du Noyau, Institut Pasteur, 75724 Paris, Cedex 15, France
3 Departamento de Bioquímica y Biología Molecular and 4 Sección de Chips de DNA Servei de Suport a la Investigació Experimental, Universitat de València, E46100 València, Spain

Correspondence to Ed Hurt: ed.hurt{at}bzh.uni-heidelberg.de

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 src1{Delta} 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.

Abbreviations used in this paper: 5-FOA, 5-fluoroorotic acid; ChIP, chromatin immunoprecipitation; HP, high phosphate; LP, low phosphate; mRNP, messenger RNP particle; MSC, Man1-Src1 C terminal; NPC, nuclear pore complex; ProtA, protein A; rDNA, ribosomal DNA; SAGA, Spt/Ada/Gcn5 acetyltransferase; TAP, tandem affinity purification; TEV, tobacco etch virus; TREX, transcription export; wt, wild type.

© 2008 Grund et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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Related In this Issue article

SRC1, central to the nuclear periphery
Richard Robinson and Ruth Williams
J. Cell Biol. 2008 182: 819. [Full Text] [PDF]



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