We have earlier unveiled mechanisms of disassembly and reformation of the nuclear envelope in cell extracts and at mitosis (Martins et al. 2003 J Cell Biol; Steen et al. 2000 J Cell Biol; ibid Steen et al. 2001 J Cell Biol). Subsequently, we developed cell extracts capable of remodeling chromatin and gene expression in purified nuclei (Landsverk et al. 2002 EMBO Rep) and in cells (Håkelien et al. 2002 Nature Biotech; Taranger et al. 2005 Mol Biol Cell; Freberg et al. 2007 Mol Biol Cell).
With the aim of identifying epigenetic determinants of mesenchymal stem cell differentiation, we have mapped various chromatin components including DNA methylation, histone modifications and histone variant H3.3 in adipose stem cells (Sørensen et al. 2010 Mol Biol Cell; Delbarre et al. 2010 Mol Biol Cell). We have through this work identified a novel pathway and new regulators of deposition of H3.3 in chromatin (Delbarre et al. 2013 Genome Res; Ivanauskiene et al. 2014 Genome Res), and a role of PML in organizing heterochromatin domains (Delbarre et al. 2017 Genome Res).
We have established chromatin immunoprecipitation (ChIP) assays for small cell numbers (Dahl and Collas 2008 Nature Protoc; Dahl et al. 2009 Genome Biol) and subsequently shown an epigenetic pre-patterning of developmental gene expression prior to onset of embryonic gene activation in zebrafish (Lindeman et al., 2011 Dev Cell; Andersen et al., 2012 Genome Biol).
We have mapped contacts of nuclear lamins with the genome during adipogenic differentiation and shown a resetting of these interactions in this process (Lund et al. 2013 Genome Res; Rønningen, Shah et al. 2015 Genome Res). To this end we have established a ChIP-seq protocol for nuclear lamins and have released an algorithm to map lamin-associated domains (LADs) and other wide genomic domains of protein enrichment (Lund et al. 2014 Nucl Acids Res). We are developing new computational platforms to model the human genome in 3D and at high resolution (Paulsen et al. 2015 PLoS Comput Biol; Sekelja et al 2016 Genome Biol; Paulsen et al. 2017 Genome Biol).