Role of histone methylation in insect development: KMT5A regulates ecdysteroid biosynthesis during metamorphosis of Tribolium castaneum

Yaoyu Jiao; Karthi Sengodan; Jiasheng Chen; Subba Reddy Palli

doi:10.1016/j.ibmb.2025.104316

Role of histone methylation in insect development: KMT5A regulates ecdysteroid biosynthesis during metamorphosis of Tribolium castaneum

Yaoyu Jiao, Karthi Sengodan, Jiasheng Chen, Subba Reddy Palli

Research output: Contribution to journal › Article › peer-review

Abstract

Methylation levels of core histones play important roles in the regulation of gene expression and impact animal development. However, the methyltransferases and demethylases that determine histone methylation levels remain largely unexplored in insects. Most of our current understanding of histone methylation comes from mammalian studies. In this study, we first identified potential histone methyltransferases and demethylases encoded in the genome of the red flour beetle Tribolium castaneum. The function of these histone methylation enzymes in the metamorphosis was investigated by knocking down genes coding for these enzymes using RNA interference (RNAi). Our results showed that a lysine methyltransferase, KMT5A, plays a critical role in T. castaneum metamorphosis by regulating the biosynthesis of ecdysteroids. Treating KMT5A-knockdown larvae with 20 hydroxyecdysone can partially rescue T. castaneum pupation. Western blot analysis showed that KMT5A catalyzes H4K20 mono-methylation. However, further studies suggest that KMT5A may regulate T. castaneum pupation through mechanisms independent of H4K20 methylation. These data uncovered the roles of histone methylation enzymes in T. castaneum metamorphosis and KMT5A as a critical regulator of ecdysteroid biosynthesis.

Original language	English
Article number	104316
Journal	Insect Biochemistry and Molecular Biology
Volume	180
DOIs	https://doi.org/10.1016/j.ibmb.2025.104316
State	Published - May 2025

Bibliographical note

Publisher Copyright:
© 2025 Elsevier Ltd

Funding

The research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM070559 and the US Department of Agriculture (under HATCH Project 2353057000 ). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the US Department of Agriculture.

Funders	Funder number
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences
National Institutes of Health (NIH)	R01GM070559
National Institutes of Health (NIH)
U.S. Department of Agriculture	2353057000
U.S. Department of Agriculture

Keywords

Demethylases
Epigenetics
Gene expression
Histone methyltransferases
RNAi

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Insect Science

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10.1016/j.ibmb.2025.104316

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title = "Role of histone methylation in insect development: KMT5A regulates ecdysteroid biosynthesis during metamorphosis of Tribolium castaneum",

abstract = "Methylation levels of core histones play important roles in the regulation of gene expression and impact animal development. However, the methyltransferases and demethylases that determine histone methylation levels remain largely unexplored in insects. Most of our current understanding of histone methylation comes from mammalian studies. In this study, we first identified potential histone methyltransferases and demethylases encoded in the genome of the red flour beetle Tribolium castaneum. The function of these histone methylation enzymes in the metamorphosis was investigated by knocking down genes coding for these enzymes using RNA interference (RNAi). Our results showed that a lysine methyltransferase, KMT5A, plays a critical role in T. castaneum metamorphosis by regulating the biosynthesis of ecdysteroids. Treating KMT5A-knockdown larvae with 20 hydroxyecdysone can partially rescue T. castaneum pupation. Western blot analysis showed that KMT5A catalyzes H4K20 mono-methylation. However, further studies suggest that KMT5A may regulate T. castaneum pupation through mechanisms independent of H4K20 methylation. These data uncovered the roles of histone methylation enzymes in T. castaneum metamorphosis and KMT5A as a critical regulator of ecdysteroid biosynthesis.",

keywords = "Demethylases, Epigenetics, Gene expression, Histone methyltransferases, RNAi",

author = "Yaoyu Jiao and Karthi Sengodan and Jiasheng Chen and Palli, \{Subba Reddy\}",

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year = "2025",

month = may,

doi = "10.1016/j.ibmb.2025.104316",

language = "English",

volume = "180",

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AU - Chen, Jiasheng

AU - Palli, Subba Reddy

PY - 2025/5

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AB - Methylation levels of core histones play important roles in the regulation of gene expression and impact animal development. However, the methyltransferases and demethylases that determine histone methylation levels remain largely unexplored in insects. Most of our current understanding of histone methylation comes from mammalian studies. In this study, we first identified potential histone methyltransferases and demethylases encoded in the genome of the red flour beetle Tribolium castaneum. The function of these histone methylation enzymes in the metamorphosis was investigated by knocking down genes coding for these enzymes using RNA interference (RNAi). Our results showed that a lysine methyltransferase, KMT5A, plays a critical role in T. castaneum metamorphosis by regulating the biosynthesis of ecdysteroids. Treating KMT5A-knockdown larvae with 20 hydroxyecdysone can partially rescue T. castaneum pupation. Western blot analysis showed that KMT5A catalyzes H4K20 mono-methylation. However, further studies suggest that KMT5A may regulate T. castaneum pupation through mechanisms independent of H4K20 methylation. These data uncovered the roles of histone methylation enzymes in T. castaneum metamorphosis and KMT5A as a critical regulator of ecdysteroid biosynthesis.

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KW - RNAi

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Role of histone methylation in insect development: KMT5A regulates ecdysteroid biosynthesis during metamorphosis of Tribolium castaneum

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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