10.6084/m9.figshare.10059869.v1 David A. Kalmbach David A. Kalmbach Schröder C. Schröder C. Klein-Hitpass L. Klein-Hitpass L. Nordström K. Nordström K. Ulz P. Ulz P. Heitzer E. Heitzer E. Speicher M.R. Speicher M.R. Rahmann S. Rahmann S. Wieczorek D. Wieczorek D. Horsthemke B. Horsthemke B. Bramswig N.C. Bramswig N.C. Supplementary Material for: Genome-Wide Analysis of the Nucleosome Landscape in Individuals with Coffin-Siris Syndrome Karger Publishers 2019 Coffin-Siris syndrome Epigenetics Monocytes NOMe-seq SWI/SNF 2019-10-28 14:54:27 Dataset https://karger.figshare.com/articles/dataset/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….