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McCauley, M.

Publications and source records attributed to McCauley, M..

2 recordsLinked to original sources

Symbiosis-driven development in an early branching metazoan

Microbes can initiate developmental gene regulatory cascades in animals. The molecular mechanisms underlying microbe-induced animal development and the evolutionary steps to integrate microbial signals into regulatory programs remain poorly understood. In the upside-down jellyfish Cassiopea xamachana, a dinoflagellate endosymbiont initiates the life stage transition from the sessile polyp to the sexual medusa. We found that metabolic products derived from symbiont carotenoids may be important to initiate C. xamachana development, in addition to expression of conserved genes involved in medusa development of non-symbiotic jellyfish. We also revealed the transcription factor COUP is expressed during metamorphosis, potentially as a co-regulator of nuclear receptor RXR. These data suggest relatively few steps may be necessary to integrate symbiont signals into gene regulatory networks and cements the role of the symbiont as a key trigger for life history transition in C. xamachana.

developmental biology↗

Protein hyperacylation links mitochondrial dysfunction with nuclear organization

Cellular metabolism is linked to epigenetics, but the biophysical effects of metabolism on chromatin structure and implications for gene regulation remain largely unknown. Here, using a broken tricarboxylic acid (TCA) cycle and disrupted electron transport chain (ETC) exemplified by succinate dehydrogenase subunit C (SDHC) deficiency, we investigated the effects of metabolism on chromatin architecture over multiple distance scales [nucleosomes ([~]102 bp), topologically-associated domains (TADs; [~]105 - 106 bp), and chromatin compartments (106 - 108 bp)]. Metabolically-driven hyperacylation of histones led to weakened nucleosome positioning in multiple types of chromatin, and we further demonstrate that lysine acylation directly destabilizes histone octamer-DNA interactions. Hyperacylation of cohesin subunits correlated with decreased mobility on interphase chromatin and increased TAD boundary strength, suggesting that cohesin is metabolically regulated. Erosion of chromatin compartment distinctions reveals metabolic regulation of chromatin liquid-liquid phase separation. The TCA cycle and ETC thus modulate chromatin structure over multiple distance scales.

cell biology↗