Changes in histone abundance and post-translational modifications in Rana [Lithobates] catesbeiana tissues during...

Amphibian metamorphosis involves thyroid hormone (TH)-dependent postembryonic remodeling of differentiated tissues as a tadpole transforms into a frog. Rana [Lithobates] catesbeiana (American bullfrog) metamorphosis can be precociously induced in premetamorphic tadpoles by treatment with exogenous TH. However, metamorphosis is temperature-dependent and does not occur at 5 °C, even with TH treatment. Remarkably, exposure to TH at 5 °C establishes a molecular memory that primes the tadpole for an accelerated metamorphosis when shifted to a permissive temperature (24 °C). Previous research suggests that histone post-translational modifications (PTMs) and the incorporation of histone variants are altered upon cold temperature exposure in the presence and absence of TH. Herein, we use mass spectrometry to analyze the histone composition of premetamorphic R. catesbeiana blood, liver, and tailfin following TH injection at a permissive temperature (24 °C), a non-permissive temperature (5 °C), and a shifted condition (5 → 24 °C). Using stringent selection criteria, we identified tissue- and temperature-specific changes in the abundance and putative PTMs of chromatin-binding proteins, including histones. Linker histone variant H1.0 abundance increased in all three tissues following TH treatment under permissive temperatures only. TH-dependent changes in the abundance of methyl-CpG binding protein 2 (MeCP2) and high mobility group (HMG) proteins were temperature- and tissue-specific. PTMs, including variations in H3K27 and H3K36 methylations in the liver, were differentially abundant following TH treatment under the different temperature conditions. We also identified newly discovered HMGB2 methylation marks that exhibited temperature-specific changes in abundance following TH treatment. These observations suggest that epigenetic variations may contribute to early TH signaling events and to molecular memory.