Ribosomal DNA copy number: a novel epigenetic modulator and platform for analyses of adaptation and sensitization to repeated chemical exposures.
Principal Investigator: Bernardo Lemos, Ph.D.
Epigenetic inheritance requires the presence of proteins and RNAs that package the target DNA into a specialized epigenetic structure that can be activated, silenced, and transmitted between generations. The ribosomal DNA (rDNA) array is a key point of epigenetic control. Ribosomal DNA arrays give origin to the nucleolus, the site of rRNA synthesis and major organizer of nuclear architecture. We have identified over 10- fold variation in ribosomal DNA copy number (CN) in humans with functional consequences to global epigenetic states. Our observations also indicate that rDNA CN is responsive to a single exposure of BPA and Chromium. However, the hypothesis that rDNA CN is modulated by the environment is novel and data on multiple exposures or repeated cycles of exposure is lacking. This system provides a novel platform for testing key ideas about epigenetic sensitization and adaptation through repeated cycles of exposure with amplification and contraction of rDNA CN. The research is a required step towards testing three novel ideas: that the rDNA is a modulator of response to exposure, that rDNA CN is itself modulated by exposure, that repeated cycles of exposure will cause dampened or amplified responses at later exposure events. The research leverages existing investments on ongoing research with new collaborations to broaden the impact of the research.
Products resulting from Hoffman support
Lou J, Yu S, Feng L, Guo X, Wang M, Branco AT, Li T, Lemos B. Environmentally induced ribosomal DNA (rDNA) instability in human cells and populations exposed to hexavalent chromium [Cr (VI)]. Environ Int. 2021 Aug;153:106525. doi: 10.1016/j.envint.2021.106525. Epub 2021 Mar 25. PMID: 33774497; PMCID: PMC8477438.
Guo X, Feng L, Lemos B, Lou J. DNA methylation modifications induced by hexavalent chromium. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2019;37(3):133-145. doi: 10.1080/10590501.2019.1592640. Epub 2019 May 13. PMID: 31084241; PMCID: PMC8479272.