A joint research group of Osaka University, Hokkaido University, Tokyo Institute of Technology, and Kyushu University is the first in the world to suppress chromosomal abnormalities in which heterochromatin of a chromosome makes a DNA repeat sequence (centromere repeat) in the centromere region a "glue". Revealed.
Chromosomal regions that are crucial for accurate chromosomal partitioning Centromeres can cause chromosomal abnormalities such as translocations that "glue" centromeres repeats.Centromeres have a heterochromatin structure in which chromatin (a structure whose basic unit is a nucleosome in which DNA is wrapped around a histone protein) is condensed, but its association with chromosomal abnormalities has not been known.
In this study, we investigated the role of heterochromatin in chromosomal stability using fission yeast with a chromatin structure similar to that of humans.As a result, it was found that gene disruption of the methylating enzyme of the lysine residue (H3K3) of histone H9, which is the basis of heterochromatin, frequently forms chromosomal abnormalities with centromere repeats as "glue".In addition, chromosomal abnormalities occurred frequently even in mutant strains in which H3K9 methylation modification did not occur.From this, it was clarified that the methylation modification of H3K9 in heterochromatin is important for the suppression of chromosomal abnormalities.
Furthermore, a detailed examination of the heterochromatin-deficient strain revealed that the transcription factor TFIIS, which promotes the elongation of transcription (a reaction of synthesizing RNA using DNA as a template), induces chromosomal abnormalities.It is known that transcription is unlikely to occur in the heterochromatin region, and the mechanism of suppressing chromosomal abnormalities mediated by transcriptional regulation of heterochromatin has been clarified.
This result is expected to lead to application to gene therapy only by chromatin control without genomic mutation.
Paper information:[Communications Biology] Heterochromatin suppresses gross chromosomal rearrangements at centromeres by repressing Tfs1 / TFIIS-dependent transcription