Rice histone H2A.X is a master regulator of development and yield
Research Summary: We show how a histone variant named H2A.X, genome’s master regulator functions in plants. We show previously unexplored roles of gene body enriched, H2A.X variant in controlling gene expression. This protein blocks another histone named H2A.W and also acts as a gatekeeper to histone mark signature.
Researcher Spotlight
Aravind M is a Ph.D. student in Dr. P.V. Shivaprasad’s lab at NCBS and he is interested in studying the epigenetic mechanisms involved in plant development and stress responses.
Linkedin aravind madhu
Twitter – @aravindmadhu41
Lab PI name: Prof. P.V. Shivaprasad, National Centre for Biological Sciences (NCBS). Tata Institute of Fundamental Research
Lab social media: @shivaprasad_pv
What was the core problem you aimed to solve with this research?
H2A.X is an important global player in DNA damage response across eukaryotes. Everyone thought its role was only in DNA damage response. We observed that it is highly decorated over gene bodies in plants and hypothesized that it must be having roles in controlling gene expression and protein production in normal unstressed conditions. We observed severe reproductive and vegetative developmental defects in H2A.X mis-expression lines where protein is either made more, or shut-off completely such as by using CRIPSR mediated double knockout (ko) plants. With these observations we tried to understand how this variant is involved in regulating development of rice plants.
How did you go about solving this problem?
We generated several mis-expression lines of H2A.X including CRIPSR mediated double knockout (ko) plants and observed severe developmental defects. We studied in depth how these gene expression changes are taking place. We found that these defects were due to higher expression of specific genes in these plants. We generated specific antibodies against rice H2A variants and characterised their binding sites for the first time in rice plants. We employed genetics, high throughput genomics and molecular biology approaches to understand the role of H2A.X in development of rice plants.
“It is extremely valuable to learn that a master regulator of this kind is contributing to yield traits. The genes under H2A.X histone variant’s control are useful candidates to improve crops.” – Prof. P.V. Shivaprasad
How would you explain your research outcomes (Key findings) to the non-scientific community?
Histone variants evolved to function as master regulators of gene expression, often in specific tissues, or in response to certain environmental stimuli or in distinct chromatin locations. This work highlights the previously unknown function of a histone 2A (H2A) variant named H2A.X in regulating the gene expression in rice plants. If the gene coding for this protein was removed, there were profound defects in root growth and partial sterility was observed. On the other hand, expressing this protein a bit more led to higher DNA damage resistance by activating key DNA damage response genes. These findings show that H2A.X is involved in maintaining genes important for both development and stress responses. Few such genes have been discovered among plants.
What are the potential implications of your findings for the field and society?
After H2A.Z, which is a well-known stress responsive H2A variant across organisms and widely used to improve crops, here we identified another H2A variant which directly influences genes that are involved in various useful traits. Since H2A.X suppresses marking of ‘active H3K4me3’ from gene bodies and it represses H2A.W and H3K9me2 repressive marks from heterochromatin regions, it can be trained to target genes of interest.
What was the exciting moment during your research?
Finding the repressive effect of H2A.X over development and yield-related genes and its competition with histone marks and histone variants was unexpected.
Paper reference: https://academic.oup.com/nar/article/54/9/gkag476/8678696.
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