Developmentally dynamic chromatin state at loci regulating interorgan communication
Interorgan communication, metabolite regulation and drug handling all require fine-tuned transport of small molecules across cellular membranes. Approximately 1000 protein-coding genes – including hundreds of solute carrier (SLC) and ATP-binding cassette (ABC) transporters as well as enzymes and transcription factors-mediate small molecule organ crosstalk via a process known as “remote sensing and signaling (RSS)”. The RSS protein coding genes greatly overlap with those regulating absorption, digestion, metabolism and excretion (ADME) of small molecule drugs. However, it is not known how chromatin and epigenetic state at these loci are coordinately regulated during the development of the liver and kidney, which control the small molecule composition of the blood, or the brain, whose physiology relies upon proper regulation of this process. Understanding how epigenetic state changes during development at these loci provides insight into how the body attains autonomous functionality. Overall design: CUT&RUN of the histone modifications H3K4me3, H3K27ac, H3K9ac, and H3K27me3 in mouse kidney, liver, and brain