Loss of a DNA binding site within the tail of prelamin A contributes to altered heterochromatin anchorage by progerin

Bruston, Francine; Delbarre, Erwan; Östlund, Cecilia; Worman, Howard J.; Buendia, Brigitte; Duband-Goulet, Isabelle

doi:10.1016/j.febslet.2010.05.032

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Volume 584, Issue 14 , Pages 2999-3004, 16 July 2010

Loss of a DNA binding site within the tail of prelamin A contributes to altered heterochromatin anchorage by progerin

Edited by Ulrike Kutay

Francine Bruston
- Laboratory of Stress and Pathologies of the Cytoskeleton, Unit of Functional and Adaptive Biology (BFA) affiliated with CNRS, Université Paris Diderot-Paris 7, 4 rue Marie-Andrée Lagroua Weill-Halle, 75205 Paris Cedex 13, France
Erwan Delbarre
- Institute of Basic Medical Sciences, Department of Biochemistry, Faculty of Medicine, University of Oslo, P.O. Box 1112, Blindern, 0317 Oslo, Norway
Cecilia Östlund
- Department of Medicine and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 W. 168th street, New York, NY 10032, USA
Howard J. Worman
- Department of Medicine and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, 630 W. 168th street, New York, NY 10032, USA
Brigitte Buendia
- Laboratory of Stress and Pathologies of the Cytoskeleton, Unit of Functional and Adaptive Biology (BFA) affiliated with CNRS, Université Paris Diderot-Paris 7, 4 rue Marie-Andrée Lagroua Weill-Halle, 75205 Paris Cedex 13, France
Isabelle Duband-Goulet
- Laboratory of Stress and Pathologies of the Cytoskeleton, Unit of Functional and Adaptive Biology (BFA) affiliated with CNRS, Université Paris Diderot-Paris 7, 4 rue Marie-Andrée Lagroua Weill-Halle, 75205 Paris Cedex 13, France
- Corresponding author. Fax: +33 1 57 27 79 69.

Received 22 March 2010; received in revised form 7 May 2010; accepted 13 May 2010. published online 24 May 2010.

Abstract

Mutations in the lamin A/C (LMNA) gene that cause Hutchinson-Gilford progeria syndrome (HGPS) lead to expression of a protein called progerin with 50 amino acids deleted from the tail of prelamin A. In cells from patients with HGPS, both the amount and distribution of heterochromatin are altered. We designed in vitro assays to ask whether such alterations might reflect changes in chromatin, DNA and/or histone binding properties of progerin compared to wild-type lamin C-terminal tails. We show that progerin tail has a reduced DNA/chromatin binding capacity and modified trimethylated H3K27 binding pattern, offering a molecular mechanism for heterochromatin alterations related to HGPS.

Structured summary

MINT-7893924, MINT-7893941, MINT-7893990, MINT-7894005, MINT-7894023, MINT-7894038: H3 (uniprotkb:Q71DI3) binds (MI:0407) to LaminA (uniprotkb:P02545) by surface plasmon resonance (MI:0107)

MINT-7893957, MINT-7893974, MINT-7894055: H3 (uniprotkb:Q71DI3) binds (MI:0407) to progerin (uniprotkb:Q6UYC3) by surface plasmon resonance (MI:0107)

Keywords: Chromatin, Histone methylation, Lamins, Premature senescence, Protein interaction

Abbreviations: AEBSF, 4-(2-aminoethyl)benzenesulfonyl fluoride, aa, amino acids, EMSA, electrophoretic mobility shift assay, GST, glutathione S-transferase, HGPS, Hutchinson-Gilford progeria syndrome, HP1, heterochromatin protein 1, LMNA, lamin A/C gene, LMNB1, lamin B1 gene, LMNB2, lamin B2 gene, NLS, nuclear localization signal