Histone's secrets unravelled
14 Sep 2017 by Evoluted New Media
Researchers in Spain have discovered why histone 1, a protein involved in gene expression, is a protective factor against DNA damage.
Researchers in Spain have discovered why histone 1, a protein involved in gene expression, is a protective factor against DNA damage.
Histones package and order DNA into structural units called nucleosomes. The scientists’ research suggests that histone 1 suppression causes both cellular damage and genomic instability.
Dr Ferran Azorin, group leader at the Institute for Research in Biomedicine, said: “Although histone 1 is a key component of chromatin, the form in which DNA is packaged inside the cell nucleus through the action of histones, there are still many questions open regarding this molecule.”
Shedding light on the histone
This study also shows that deregulation of a commonly supressed region of chromatin, known as heterochromatin, leads to defects in information transcription, giving rise to the accumulation of DNA and RNA hybrids – R-loops – involved in genetic damage.
Dr Azorin said: “Regarding the other histones, which are major proteins in the regulation of gene expression, we know which enzymes modify them, their functions, and how they are regulated. But for some reason, the functions of histone 1 have not been addressed.”
Using fruit flies (Drosophila melanogaster), researchers discovered histone 1 not only suppressed but actively assisted in the removal of R loops. Drosophila has one variant of this protein – humans possess up to seven – making them an ideal subject for this research. After scientists removed histone 1 from the precursor structure of a fruit fly’s wings, it was born alive – but wingless. This suggested to the scientists that histone 1 removal caused the death of all cell precursors for this tissue – if removed from the entire fly, the embryo dies.
Scientists were also able to prove that histone 1 is not a global repressor of expression. Jordi Bernués, an associate researcher in Azorin’s research group, said that the effect of removing histone 1 on gene expression is very weak as its expression alters only 5% of genes.
Histone 1 deficiency has also been linked to genomic instability present in tumour cells. The scientists aim to further study histone 1’s functions, identifying associated proteins and modifying enzymes as well as cell signalling pathways. The paper was published in Nature Communications.
