TY - JOUR TI - Caenorhabditis elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor AU - Giese, Gabrielle E AU - Walker, Melissa D AU - Ponomarova, Olga AU - Zhang, Hefei AU - Li, Xuhang AU - Minevich, Gregory AU - Walhout, Albertha JM A2 - Hobert, Oliver A2 - Barkai, Naama VL - 9 PY - 2020 DA - 2020/10/05 SP - e60259 C1 - eLife 2020;9:e60259 DO - 10.7554/eLife.60259 UR - https://doi.org/10.7554/eLife.60259 AB - Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as ‘B12-mechanism-I’. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as ‘B12-mechanism-II’. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires nhr-114 to activate Met/SAM cycle gene expression, the vitamin B12 transporter, pmp-5, and adjust influx and efflux of the cycle by activating msra-1 and repressing cbs-1, respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime. KW - methionine/sam cycle KW - nuclear hormone receptor KW - vitamin B12 KW - transcription factors KW - metabolism JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -