Epigenetic Effects and Potential Contributions of m6A Modification to Mammary Gland Development and Lactation of Dairy Goats Explored via MeRIP-seq

TL;DR

This study explores how m6A RNA methylation affects mammary gland development and lactation in dairy goats, identifying key genes and pathways involved.

Contribution

The study reveals gene-specific and context-specific roles of m6A modification in dairy goat mammary gland development and lactation.

Findings

1539 differentially methylated genes were identified, enriched in pathways like Toll-like receptor and MAPK signaling.

150 genes were negatively regulated by m6A modifications, with five key genes (PPARG, HSPA2, CDK5, ACTB, NOTCH3) consistently dysregulated.

m6A modification influences mammary gland development and lactation through gene-specific regulation.

Abstract

To investigate the role of m6A methylation modification in the development and lactation ability of dairy goat mammary glands, tissue samples were collected during the early period (20 days postpartum), peak (90 days postpartum), and late period (210 days postpartum. MeRIP-seq combined with RNA-seq was used to explore m6A methylation modification events. There were 1638 differential peaks in the MeRIP-seq data, across 1539 differentially methylated genes, which were enriched in the Toll-like receptor signaling pathway, MAPK and other pathways related to mammary gland development and lactation. A conjoint analysis of RNA-seq and MeRIP-seq revealed that, among the 179 common DEGs identified, 150 genes exhibited negative regulation as a results of m6A modifications. Five key DEGs—PPARG, HSPA2, CDK5, ACTB, and NOTCH3—were consistently dysregulated in both groups. In summary, m6A modification involves pathways related to mammary gland development and lactation in ways that are gene and context specific. This study provides new insights into the physiological and epigenetic regulation mechanisms of mammary gland development and lactation in dairy goats.

To date, more than 170 chemical modifications have been identified in RNA. m6A (N6-methyladenine) RNA methylation is the most abundant form of mRNA modification in eukaryotes, playing an important role in RNA post-transcriptional processes. To investigate the function of m6A methylation modification in the development and lactation of dairy goat mammary glands, mammary gland tissue samples were collected in the early (20 days postpartum), peak (90 days postpartum), and late period (210 days postpartum) of three dairy goats. MeRIP-seq and RNA-seq were used to explore m6A methylation modification events. We identified 1638 differential peaks in the MeRIP-seq data across 1539 differentially methylated genes, which were enriched in ribosome biogenesis in eukaryotes, Toll-like receptor signaling pathway, TNF signaling pathway, MAPK, and other pathways related to mammary gland development and lactation. A conjoint analysis revealed that 179 common differential expressed genes were obtained, of which 150 were negatively regulated by their m6A modifications, while 5 common differentially expressed genes—PPARG, HSPA2, CDK5, ACTB and NOTCH3, were screened out in the two groups. In conclusion, m6A modification involves the pathways related to mammary gland development and lactation by modifying gene expression. This studyprovides new insights into m6A epigenetic regulation, mammary epithelial gene networks, and actionable molecular targets for high-value dairy product production and the breeding of new varieties.

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