title: A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha.
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.
authors.affiliation: Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria;
authors.forename: Kevin
authors.initials: K
authors.lastname: Gesson
authors.affiliation: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories (MFPL), Medical University of Vienna and University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria;
authors.forename: Philipp
authors.initials: P
authors.lastname: Rescheneder
authors.affiliation: Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria;
authors.forename: Michael P
authors.initials: MP
authors.lastname: Skoruppa
authors.affiliation: Center for Integrative Bioinformatics Vienna, Max F. Perutz Laboratories (MFPL), Medical University of Vienna and University of Vienna, Vienna Biocenter (VBC), A-1030 Vienna, Austria; Bioinformatics and Computational Biology, Faculty of Computer Science, University of Vienna, A-1030 Vienna, Austria.
authors.forename: Arndt
authors.initials: A
authors.lastname: von Haeseler
authors.affiliation: Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria;
authors.forename: Thomas
authors.initials: T
authors.lastname: Dechat
authors.affiliation: Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria;
authors.forename: Roland
authors.identifier: http://orcid.org/0000-0003-4734-4647
authors.initials: R
authors.lastname: Foisner
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D044127:Epigenesis, Genetic; D022041:Euchromatin / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D015321:Gene Rearrangement; D006570:Heterochromatin / Q000235:genetics* / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000378:metabolism; D034904:Lamin Type A / Q000378:metabolism*; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D004268:DNA-Binding Proteins; D022041:Euchromatin; D006570:Heterochromatin; D006657:Histones; D034904:Lamin Type A; D008565:Membrane Proteins; C093413:lamina-associated polypeptide 2