Rapid response of gene expression in altered gravity is associated with changes in 3D chromatin conformation

The molecular principles involved in the transduction of gravity changes Into cellular response and adaptation processes are largely unknown. We have shown in human Jurkat T cells that genes are differentially regulated in cluster structures ("gravity-responsive chromosomal regions", GRCR5) upon gravity change. Combined with high-throughput chromatin conformation capture (Hi-C) analysis (Hi-C), we Identified a highly significant association of GRCRs with structural 3D chromatin changes that colocalize primarily on the small chromosomes (chr16-chr22). We further found evidence fora mechanistic link between splicing processes and differential gene expression under altered gravity. Thus, we found first evidence that gravitational changes are transmitted to the nucleus, where they induce 3D chromosome conformational changes associated with a rapid transcriptional response. We suggest that the rapid genomic response to altered gravitational forces is specifically encoded in the spatial chromatin organization.