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1. Roadmap on plasticity and epigenetics in cancer

   https://doi.org/10.1088/1478-3975/ac4ee2  

   Foo, Jasmine; Basanta, David; Rockne, Russell C; Strelez, Carly; Shah, Curran; Ghaffarian, Kimya; Mumenthaler, Shannon M; Mitchell, Kelly; Lathia, Justin D; Frankhouser, David; et al (April 2022, Physical Biology)

   Abstract The role of plasticity and epigenetics in shaping cancer evolution and response to therapy has taken center stage with recent technological advances including single cell sequencing. This roadmap article is focused on state-of-the-art mathematical and experimental approaches to interrogate plasticity in cancer, and addresses the following themes and questions: is there a formal overarching framework that encompasses both non-genetic plasticity and mutation-driven somatic evolution? How do we measure and model the role of the microenvironment in influencing/controlling non-genetic plasticity? How can we experimentally study non-genetic plasticity? Which mathematical techniques are required or best suited? What are the clinical and practical applications and implications of these concepts? 

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2. Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria

   https://doi.org/10.1073/pnas.2002933117  

   Wu, Xiaolin; Cao, Bo; Aquino, Patricia; Chiu, Tsu-Pei; Chen, Chao; Jiang, Susu; Deng, Zixin; Chen, Shi; Rohs, Remo; Wang, Lianrong; et al (June 2020, Proceedings of the National Academy of Sciences)

   Phosphorothioate (PT) DNA modifications—in which a nonbonding phosphate oxygen is replaced with sulfur—represent a widespread, horizontally transferred epigenetic system in prokaryotes and have a highly unusual property of occupying only a small fraction of available consensus sequences in a genome. UsingSalmonella entericaas a model, we asked a question of fundamental importance: How do the PT-modifying DndA-E proteins select their G_PSAAC/G_PSTTC targets? Here, we applied innovative analytical, sequencing, and computational tools to discover a novel behavior for DNA-binding proteins: The Dnd proteins are “parked” at the G^6mATC Dam methyltransferase consensus sequence instead of the expected GAAC/GTTC motif, with removal of the^6mA permitting extensive PT modification of GATC sites. This shift in modification sites further revealed a surprising constancy in the density of PT modifications across the genome. Computational analysis showed that GAAC, GTTC, and GATC share common features of DNA shape, which suggests that PT epigenetics are regulated in a density-dependent manner partly by DNA shape-driven target selection in the genome. 

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3. Epigenetics and genome stability

   https://doi.org/10.1007/s00335-020-09836-2  

   Feng, Justina X.; Riddle, Nicole C. (June 2020, Mammalian Genome)
4. Marine Environmental Epigenetics

   https://doi.org/10.1146/annurev-marine-010318-095114  

   Eirin-Lopez, Jose M.; Putnam, Hollie M. (June 2018, Annual Review of Marine Science)
5. Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development.

   https://doi.org/10.3389/fcvm.2021.668252  

   Deegan, Daniel F; Nigam, Priya; Engel, N (May 2021, Frontiers in cardiovascular medicine)

   The democratization of genomic technologies has revealed profound sex biases in expression patterns in every adult tissue, even in organs with no conspicuous differences, such as the heart. With the increasing awareness of the disparities in cardiac pathophysiology between males and females, there are exciting opportunities to explore how sex differences in the heart are established developmentally. Although sexual dimorphism is traditionally attributed to hormonal influence, expression and epigenetic sex biases observed in early cardiac development can only be accounted for by the difference in sex chromosome composition, i.e., XX in females and XY in males. In fact, genes linked to the X and Y chromosomes, many of which encode regulatory factors, are expressed in cardiac progenitor cells and at every subsequent developmental stage. The effect of the sex chromosome composition may explain why many congenital heart defects originating before gonad formation exhibit sex biases in presentation, mortality, and morbidity. Some transcriptional and epigenetic sex biases established soon after fertilization persist in cardiac lineages, suggesting that early epigenetic events are perpetuated beyond early embryogenesis. Importantly, when sex hormones begin to circulate, they encounter a cardiac genome that is already functionally distinct between the sexes. Although there is a wealth of knowledge on the effects of sex hormones on cardiac function, we propose that sex chromosome-linked genes and their downstream targets also contribute to the differences between male and female hearts. Moreover, identifying how hormones influence sex chromosome effects, whether antagonistically or synergistically, will enhance our understanding of how sex disparities are established. We also explore the possibility that sexual dimorphism of the developing heart predicts sex-specific responses to environmental signals and foreshadows sex-biased health-related outcomes after birth. 

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