10.6084/m9.figshare.10059869.v1 David A. Kalmbach Schröder C. Klein-Hitpass L. Nordström K. Ulz P. Heitzer E. Speicher M.R. Rahmann S. Wieczorek D. Horsthemke B. Bramswig N.C. Supplementary Material for: Genome-Wide Analysis of the Nucleosome Landscape in Individuals with Coffin-Siris Syndrome 2019 Karger Publishers Coffin-Siris syndrome Epigenetics Monocytes NOMe-seq SWI/SNF 2019-10-28 14:54:27 article https://karger.figshare.com/articles/Supplementary_Material_for_Genome-Wide_Analysis_of_the_Nucleosome_Landscape_in_Individuals_with_Coffin-Siris_Syndrome/10059869 The switch/sucrose non-fermenting (SWI/SNF) complex is an ATP-dependent chromatin remodeller that regulates the spacing of nucleosomes and thereby controls gene expression. Heterozygous mutations in genes subunits of the SWI/SNF complex have been reported in individuals with Coffin-Siris syndrome (CSS), with the majority of the mutations in <i>ARID1B</i>. CSS is a rare congenital disorder characterized by facial dysmorphisms, digital anomalies, and variable intellectual disability. We hypothesized that mutations in genes encoding subunits of the ubiquitously expressed SWI/SNF complex may lead to alterations of the nucleosome profiles in different cell types. We performed the first study on CSS-patient samples and investigated the nucleosome landscapes of cell-free DNA (cfDNA) isolated from blood plasma by whole-genome sequencing. In addition, we studied the nucleosome landscapes of CD14<sup>+</sup> monocytes from CSS-affected individuals by nucleosome occupancy and methylome-sequencing (NOMe-seq) as well as their expression profiles. In cfDNA of CSS-affected individuals with heterozygous <i>ARID1B</i> mutations, we did not observe major changes in the nucleosome profile around transcription start sites. In CD14<sup>+</sup> monocytes, we found few genomic regions with different nucleosome occupancy when compared to controls. RNA-seq analysis of CD14<sup>+</sup> monocytes of these individuals detected only few differentially expressed genes, which were not in proximity to any of the identified differential nucleosome-depleted regions. In conclusion, we show that heterozygous mutations in the human SWI/SNF subunit ARID1B do not have a major impact on the nucleosome landscape or gene expression in blood cells….