Cells break down sugar to release energy, and its products, such as acetyl-CoA and lactate, are also the raw material for histone tags. In yeast, a rise in acetyl-CoA switches on growth genes by acetylating their histones (Cai et al. 2011); in human cells, acetyl tags follow the supply of acetyl-CoA (Wellen et al. 2009). In 2019, lactate was found to become a histone tag of its own, lactylation (Zhang et al. 2019). Strong evidence: Several independent studies agree.
Gut microbes join in: in mice, molecules made by gut bacteria change histone marks across the body (Krautkramer et al. 2016). Strong evidence: Several independent studies agree. So what an organism eats, and the microbes it lives with, can reach its chromatin. This is the heart of my current project.
Genes respond. Tagged spools loosen and genes nearby can be read. When fuel runs low, eraser enzymes remove tags. So what a cell eats can change which of its genes are used.
Step inside a nucleus
Real nucleosome structures arranged into a chromatin fibre, with lactate drifting by. It works in the browser; on a VR headset you can step inside. The arrangement and the lactate are an artist’s impression.
Step inside a nucleus
Drag to look around. With a VR headset, an “Enter VR” button appears.
In my research: Lactate, histone marks and the embryo’s first genes →
Sources
- Cai L, Sutter BM, Li B, Tu BP (2011) Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Molecular Cell 42:426–437. doi:10.1016/j.molcel.2011.05.004
- Wellen KE, et al. (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324:1076–1080. doi:10.1126/science.1164097
- Zhang D, et al. (2019) Metabolic regulation of gene expression by histone lactylation. Nature 574:575–580. doi:10.1038/s41586-019-1678-1
- Krautkramer KA, et al. (2016) Diet–microbiota interactions mediate global epigenetic programming in multiple host tissues. Molecular Cell 64:982–992. doi:10.1016/j.molcel.2016.10.025