shifts were linked to reversible and gene-expression changes in the hypothalamus of ovariectomized, estradiol-treated ewes.
Evidence
An integrated whole-genome methylome and transcriptome study of sheep hypothalamic tissue across seven photoperiod time points found dynamic methylation changes, a possible transition around 15 days after switching from short to long days, and overlapping genes in synapse development, thyroid hormone signaling, and circadian rhythm pathways.
Caveat
The work used a controlled ewe model and omics associations, so it does not prove which methylation changes drive seasonal reproduction.
Simplified
BACKGROUND: Sheep are short-day breeder, and their reproductvie activity can be activated by short , but the regulatory mechanism remains unclear. In this study, hypothalamic tissues were collected from ovariectomized and estradiol-treated (OVX + E) Sunite ewes exposed to artificial short-day (SP) and long-day (LP) photoperiods. Integrated whole-genome and transcriptomic analyses were performed to elucidate the regulatory mechanisms underlying photoperiod-mediated seasonal reproduction. 2
RESULTS: The DNA methylation profiles of the hypothalamus were examined, and whole-genome single-base resolution methylome maps of the sheep hypothalamus were generated across seven time points under various photoperiod treatments. The results revealed that photoperiod-induced changes in genome-wide DNA methylation constitute a dynamic and reversible regulatory process, with a potential transition point occurring approximately 15 days after the switch from SP to LP. Following integrated analysis of differentially methylated regions-related genes (DMRGs) and differentially expressed genes (DEGs), it showed that the DNA methylation levels before the transcription start site (TSS) of the overlapping gene were different, and a negative correlation between gene expression levels and mCG levels in gene promoters was found (P < 0.01). Functional analysis of the overlapping genes revealed that pathways involved in synapse development, thyroid hormone signaling, and circadian rhythm were regulated by photoperiod-induced DNA methylation, thereby influencing hypothalamic function in photoperiod-dependent seasonal reproduction.
CONCLUSION: This study generated the whole-genome single-base resolution DNA methylome maps of sheep hypothalamus under different photoperiods, and elucidated the regulatory relationship between DNA methylation and photoperiod-dependent seasonal reproduction in sheep hypothalamus tissues. Our findings provided a valuable resource for further research on the underlying mechanisms of the hypothalamic-regulated reproductive seasonality in sheep.
Key numbers
15 days
Transition Point Timing
Transition point for changes after switch from short to long.
P < 0.01
Negative Correlation
Statistical significance of the correlation between gene expression and mCG levels.
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