Assoziation schneller Reaktionen der Genexpression mit Änderungen der 3D-Chromatinkonformation in veränderter Schwerkraft

ZUSAMMENFASSUNG

Die molekularen Prinzipien bei der Transduktion von Schwerkraftänderungen in zelluläre Antwort- und Anpassungsprozesse sind bisher weitgehend unbekannt. Wir konnten in humanen Jurkat-T-Zellen zeigen, dass Gene bei veränderter Schwerkraft in Clusterstrukturen („gravity-responsive chromosomal regions“, GRCRs) differenziell reguliert werden. Durch Kombination mit Hochdurchsatz-Chromatin-Konformationsanalysen (Hi-C) konnte eine hochsignifikante Assoziation von GRCRs mit strukturellen 3D-Chromatinveränderungen identifiziert werden, die vor allem auf den kleinen Chromosomen (chr16–chr22) kolokalisieren. Wir fanden weiterhin Hinweise auf einen mechanistischen Zusammenhang zwischen Spleißprozessen und differenzieller Genexpression bei veränderter Schwerkraft. Somit haben wir erste Belege dafür gefunden, dass Änderungen der Schwerkraft in den Zellkern übertragen werden und dort 3D-Chromosomen-Konformationsänderungen hervorrufen, die mit einer schnellen Transkriptionsantwort verbunden sind. Wir vermuten, dass die schnelle genomische Antwort auf veränderte Gravitationskräfte in der Organisation des Chromatins spezifisch codiert ist.

ABSTRACT

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”, GRCRs) 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 for a 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.

Key words

microgravity - gene expression - chromatin - adaptation

Publication History

Article published online:
10 October 2022

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