A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha

Kevin Gesson; Philipp Rescheneder; Michael P. Skoruppa; Arndt von Haeseler; Thomas Dechat; Roland Foisner

doi:10.1101/gr.196220.115

A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha

¹Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria;
²Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories (MFPL), Medical University of Vienna and University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria;
³Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, A-1030 Vienna, Austria

Corresponding author: roland.foisner{at}meduniwien.ac.at

↵4 These authors contributed equally to this work.

Abstract

Lamins are components of the peripheral nuclear lamina and interact with heterochromatic genomic regions, termed lamina-associated domains (LADs). In contrast to lamin B1 being primarily present at the nuclear periphery, lamin A/C also localizes throughout the nucleus, where it associates with the chromatin-binding protein lamina-associated polypeptide (LAP) 2 alpha. Here, we show that lamin A/C also interacts with euchromatin, as determined by chromatin immunoprecipitation of euchromatin- and heterochromatin-enriched samples. By way of contrast, lamin B1 was only found associated with heterochromatin. Euchromatic regions occupied by lamin A/C overlap with those bound by LAP2alpha, and lack of LAP2alpha in LAP2alpha-deficient cells shifts binding of lamin A/C toward more heterochromatic regions. These alterations in lamin A/C-chromatin interactions correlate with changes in epigenetic histone marks in euchromatin but do not significantly affect gene expression. Loss of lamin A/C in heterochromatic regions in LAP2alpha-deficient cells, however, correlated with increased gene expression. Our data show a novel role of nucleoplasmic lamin A/C and LAP2alpha in regulating euchromatin.

Footnotes

[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.196220.115.
Freely available online through the Genome Research Open Access option.

Received June 23, 2015.
Accepted January 19, 2016.

This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.