Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kalmbach, A; Schröder, C; Klein-Hitpass, L; Nordström, K; Ulz, P; Heitzer, E; Speicher, MR; Rahmann, S; Wieczorek, D; Horsthemke, B; Bramswig, NC.
Genome-Wide Analysis of the Nucleosome Landscape in Individuals with Coffin-Siris Syndrome.
Cytogenet Genome Res. 2019; 159(1): 1-11.
Doi: 10.1159/000503266
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- Co-Autor*innen der Med Uni Graz
- Heitzer Ellen
- Speicher Michael
- Ulz Peter
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- Abstract:
- 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 encoding subunits of the SWI/SNF complex have been reported in individuals with Coffin-Siris syndrome (CSS), with the majority of the mutations in ARID1B. 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+ 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 ARID1B mutations, we did not observe major changes in the nucleosome profile around transcription start sites. In CD14+ monocytes, we found few genomic regions with different nucleosome occupancy when compared to controls. RNA-seq analysis of CD14+ 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. This might be due to functional redundancy, cell-type specificity, or alternative functions of ARID1B. © 2019 S. Karger AG, Basel.
- Find related publications in this database (Keywords)
- Epigenetics
- Monocytes
- NOMe-seq
- SWI
- SNF
- Coffin-Siris syndrome