chromatin 3D structure in human donor chorion cells

Trisomy is the presence of one extra copy of an entire chromosome or its part in a cell nucleus. In humans, autosomal trisomies are associated with severe developmental abnormalities leading to embryonic lethality, miscarriage or pronounced deviations of various organs and systems at birth. Trisomies are characterized by alterations in gene expression level not exclusively on the trisomic chromosome, but throughout the genome. Here, we applied high-throughput chromo-some conformation capture technique (Hi-C) to study chromatin 3D structure in human donor chorion cells carrying additional chromosome 13 (Patau syndrome), chromosome 16 (the most common trisomy), and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). The presence of extra chromosomes 13 and 16, but not 18, results in systematic changes of contact frequencies between small and large chromosomes. Analyzing the behavior of individual chro-mosomes, we determined that a limited number of chromosomes change their contact patterns stochastically in trisomic cells, and that it could be linked to LAD and gene content. We also found that genome regions which are more compacted in trisomic cells are significantly enriched in housekeeping genes that potentially suggest the decrease of chromatin accessibility and tran-scription level. These results provide a framework for understanding the mechanisms of pan-genome transcription dysregulation in trisomies in the context of chromatin spatial organi-zation. Overall design: high-throughput chromosome conformation capture technique (Hi-C) to study chromatin 3D structure in human donor chorion cells carrying additional chromosome 13 (Patau syndrome), chromosome 16 (the most common trisomy), and in cultured fibroblasts with extra chromosome 18 (Edwards syndrome). Please note that processed data file generated from both samples (e.g. G and Y, I and II, a and b) is linked to the corresponding G, I, and a sample records.