A recent international study led by Akihisa Osakabe and Yoshimasa Takizawa from the University of Tokyo has illuminated the molecular processes in thale cresses (Arabidopsis thaliana) through which the DDM1 (Decreased in DNA Methylation 1) protein inhibits the transcription of mobile genetic elements known as ‘jumping genes.’ DDM1 facilitates the deposition of chemical marks that suppress transcription by making ‘jumping genes’ more accessible. As a similar variant of this protein is present in humans, this discovery sheds light on genetic disorders caused by mutations in these ‘jumping genes.’ The research findings have been published in the journal Nature Communications.
While we often describe DNA as a “string,” in reality, it resembles a complex “string ball” within a cell, with intricate looping patterns. The fundamental unit is a nucleosome, composed of DNA coiled around histone proteins. Transposons, genes capable of moving within the genome, are nestled within nucleosomes, hindering the cell from depositing chemical marks that suppress their transcription. DDM1 is a protein recognized for upholding these suppressive chemical marks, yet the mechanism by which it accesses transposons hidden within nucleosomes has remained unclear.
“‘Jumping genes’ are intriguing,” says Osakabe, the lead author of the study, “as they can bring about significant genomic alterations, both beneficial and detrimental. Examining how proteins like DDM1 regulate these genes not only enhances our comprehension of fundamental life mechanisms but also holds practical significance.”
The researchers employed cryo-electron microscopy, a technique capable of visualizing structures at almost atomic scales, to examine the DDM1 protein and DNA arrangement within the nucleosome.
“The intricate structures of DDM1 and the nucleosome were truly captivating to witness,” recollects Osakabe. “The mechanism by which DDM1 unfolds the nucleosome was particularly surprising. Despite the challenges in capturing these structures, witnessing the outcomes validated all the hard work.”
The high-resolution images illustrated the precise binding sites of DDM1 on the DNA within the nucleosome. Consequently, the specific binding site, typically responsible for nucleosome closure, became more malleable, permitting the deposition of suppressive chemical marks that impede transposon transcription.
Although seemingly subtle, this detail could mark the onset of significant advancements.
“The human counterpart of DDM1, known as HELLS, functions analogously,” reveals Osakabe. “In the foreseeable future, such revelations could pave the way for novel treatments for genetic ailments in humans stemming from analogous genes. Furthermore, this newfound knowledge offers insights into how plants and other organisms regulate their DNA, potentially enhancing our agricultural yields and enabling the development of innovative biotechnologies.”
