S-ADENOSYLMETHIONINE SYNTHASES DIFFERENTIALLY MODULATE INHERITED HISTONE H3K4 METHYLATION AND DEVELOPMENTAL DELAY IN CAENORHABDITIS ELEGANS

Author

• Sundas H. Johnson, Kennesaw State UniversityFollow

Semester of Graduation

Spring 2026

Degree Type

Thesis

Degree Name

Masters in Integrative Biology

Department

Molecular and Cellular Biology

Committee Chair/First Advisor

Brandon Carpenter

Second Advisor

Joana Wardwell-Ozgo

Third Advisor

Whitney Preisser

Abstract

Epigenetic mechanisms play a crucial role in regulating gene expression and ensuring proper cellular differentiation and development. Histone methylation, particularly the interplay between activating (H3K4me) and repressive (H3K9me) marks, dictates chromatin accessibility and transcriptional activity. This study explores the significance of histone methylation dynamics in Caenorhabditis elegans (C. elegans), focusing on the roles of SPR-5 and MET-2 epigenetic reprogramming. SPR-5, an H3K4 demethylase, and MET-2, an H3K9 methyltransferase, act synergistically to reestablish a transcriptionally ground state during germline transmission, ensuring developmental viability. Loss of SPR-5; MET-2 maternal reprogramming leads to the inappropriate inheritance of H3K4me1/2 and ectopic expression of germline genes in somatic tissues. The ectopic germline gene expression in the soma of spr-5; met-2 mutant progeny causes a wide range of somatic defects, including developmental delay and sterility. Additionally, S-adenosylmethionine synthetases (SAMS) regulate histone methylation by modulating methyl donor availability, linking metabolic states to epigenetic control. However, whether SAMS affect the inappropriately inherited H3K4me1/2 methylation and developmental delay of spr-5; met-2 mutants has not been examined. To test this, we knockdown sams-1 and sams-4 in spr-5; met-2 mutants using RNA interference and examined developmental progression. We found that without choline supplementation, sams-4 knockdown exacerbates developmental delay in spr-5; met-2 mutants, with an even more pronounced delay observed following sams-1 knockdown. Notably, choline supplementation partially rescues the developmental delay of spr-5; met-2 mutant progeny upon sams-4 knockdown while sams-1 knockdown exacerbates the spr-5; met-2 developmental delay like what we observe without choline supplementation. Together, our work provides mechanistic insight into how metabolic regulators, such as SAMS, influence inherited chromatin states and development.