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Changes in melanocyte RNA and DNA methylation favour pheomelanin synthesis and may avoid systemic oxidative stress after dietary cysteine supplementation in birds
Author(s) -
RodríguezMartínez Sol,
Márquez Rafael,
Inácio Ângela,
Galván Ismael
Publication year - 2019
Publication title -
molecular ecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.619
H-Index - 225
eISSN - 1365-294X
pISSN - 0962-1083
DOI - 10.1111/mec.15024
Subject(s) - cysteine , biology , gclc , oxidative stress , biochemistry , epigenetics , melanocyte , dna methylation , microbiology and biotechnology , gene , gene expression , genetics , downregulation and upregulation , enzyme , melanoma
Cysteine plays essential biological roles, but excessive amounts produce cellular oxidative stress. Cysteine metabolism is mainly mediated by the enzymes cysteine dioxygenase and γ‐glutamylcysteine synthetase, respectively coded by the genes CDO1 and GCLC . Here we test a new hypothesis posing that the synthesis of the pigment pheomelanin also contributes to cysteine homeostasis in melanocytes, where cysteine can enter the pheomelanogenesis pathway. We conducted an experiment with the Eurasian nuthatch Sitta europaea , a bird producing large amounts of pheomelanin for feather pigmentation, to investigate if melanocytes show epigenetic lability under exposure to excess cysteine. We increased systemic cysteine levels in nuthatches by supplementing them with dietary cysteine during growth. In feather melanocytes this led to the downregulation of genes involved in intracellular cysteine metabolism ( GCLC ), cysteine transport to the cytosol from the extracellular medium ( Slc7a11 ) and from melanosomes ( CTNS ), and regulation of tyrosinase activity ( MC1R and ASIP ). These changes were mediated by increases in DNA m 5 C in all genes except Slc7a11 , which experienced RNA m 6 A depletion. Birds supplemented with cysteine synthesized more pheomelanin than controls, but did not suffer higher systemic oxidative stress. These results suggest that excess cysteine activates an epigenetic mechanism that favours pheomelanin synthesis and may protect against oxidative stress.