N-alpha-acetyltransferase 40 modulates ecdysteroid action through chromatin accessibility changes near the promoters of 20-hydroxyecdysone response genes in Tribolium Castaneum TcA cells

Surjeet Kumar Arya; Subba Reddy Palli

doi:10.1016/j.ibmb.2025.104285

N-alpha-acetyltransferase 40 modulates ecdysteroid action through chromatin accessibility changes near the promoters of 20-hydroxyecdysone response genes in Tribolium Castaneum TcA cells

Surjeet Kumar Arya
, Subba Reddy Palli

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

Abstract

Changes in chromatin accessibility leading to altered gene expression play critical roles in cellular response to environmental signals. The function of N-alpha-acetyltransferase 40 (NAA40) in modulating chromatin accessibility and transcriptional regulation of 20-hydroxyecdysone (20E) response in Tribolium castaneum (TcA) cells was investigated. RNA interference (RNAi) was used to knockdown NAA40, and ATAC and RNA sequencing were used to examine changes in chromatin accessibility and gene expression in TcA cells exposed to 20E. ATAC-seq data revealed chromatin accessibility patterns between NAA40 knockdown and control cells exposed to 20E. Significant differences were detected in chromatin accessibility at transcription start sites (TSS) and promoter regions between dsNAA40 or dsGFP-treated cells exposed to 20E. Differential peak analysis identified many regions in the genome with altered chromatin accessibility upon NAA40 knockdown or 20E treatment, suggesting that NAA40 plays a critical role in 20E regulation of gene expression by modifying chromatin accessibility near the promoters of genes involved in 20E action. RNA sequence data analysis revealed changes in the expression of 20E response genes after NAA40 knockdown or 20E treatment. Comparison of ATAC-seq and RNA-seq data showed a correlation between chromatin accessibility and transcriptional changes of 20E response genes such as E74 and E75. Our results demonstrate that NAA40 affects chromatin dynamics and transcriptional regulation in modulating 20E response, increasing our understanding of the molecular mechanisms underlying the hormonal regulation of gene expression.

Original language	English
Article number	104285
Journal	Insect Biochemistry and Molecular Biology
Volume	179
DOIs	https://doi.org/10.1016/j.ibmb.2025.104285
State	Published - Apr 2025

Bibliographical note

Publisher Copyright:
© 2025 Elsevier Ltd

Funding

Epigenetic modifications, which include DNA methylation, histone modifications, and chromatin remodeling, play pivotal roles in regulating gene expression during insect development (Glastad et al., 2019; Roy and Palli, 2018; Yang et al., 2021). These modifications influence chromatin structure, thereby controlling access to transcriptional machinery and modulating the expression of key developmental genes. Acetylation of histones, in particular, is known to loosen chromatin, facilitating transcription factor binding, while deacetylation compacts chromatin, reducing gene expression. In insects, these processes are tightly linked to hormone action, with juvenile hormone (JH) and ecdysone being the two primary hormones orchestrating developmental transitions (De Loof et al., 2013; Gaddelapati et al., 2024; George and Palli, 2020; Mello et al., 2014; Roy and Palli, 2018; Yuan et al., 2024). The interplay between these hormones ensures that developmental transitions occur in response to external and internal cues. Epigenetic regulation has emerged as a key mediator of hormone action. For instance, studies have shown that the two key developmental hormones, JH and 20E, induce the expression of epigenetic regulators HATs and HDACs, and these enzymes, in turn, modulate the action of these hormones by regulating the expression of key genes coding for transcription factors that mediate the action of these hormones (Bodai et al., 2012; Gaddelapati et al., 2024; Lee and Grant, 2019; Mazina and Vorobyeva, 2019; Roy and Palli, 2018; Saha and Pahan, 2006; Xu et al., 2018; Yamanaka et al., 2013).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
U.S. Department of Agriculture	2353057000

Keywords

ATAC-Seq
And RNA-Seq
Chromatin
Ecdysone

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Insect Science

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10.1016/j.ibmb.2025.104285

Cite this

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title = "N-alpha-acetyltransferase 40 modulates ecdysteroid action through chromatin accessibility changes near the promoters of 20-hydroxyecdysone response genes in Tribolium Castaneum TcA cells",

abstract = "Changes in chromatin accessibility leading to altered gene expression play critical roles in cellular response to environmental signals. The function of N-alpha-acetyltransferase 40 (NAA40) in modulating chromatin accessibility and transcriptional regulation of 20-hydroxyecdysone (20E) response in Tribolium castaneum (TcA) cells was investigated. RNA interference (RNAi) was used to knockdown NAA40, and ATAC and RNA sequencing were used to examine changes in chromatin accessibility and gene expression in TcA cells exposed to 20E. ATAC-seq data revealed chromatin accessibility patterns between NAA40 knockdown and control cells exposed to 20E. Significant differences were detected in chromatin accessibility at transcription start sites (TSS) and promoter regions between dsNAA40 or dsGFP-treated cells exposed to 20E. Differential peak analysis identified many regions in the genome with altered chromatin accessibility upon NAA40 knockdown or 20E treatment, suggesting that NAA40 plays a critical role in 20E regulation of gene expression by modifying chromatin accessibility near the promoters of genes involved in 20E action. RNA sequence data analysis revealed changes in the expression of 20E response genes after NAA40 knockdown or 20E treatment. Comparison of ATAC-seq and RNA-seq data showed a correlation between chromatin accessibility and transcriptional changes of 20E response genes such as E74 and E75. Our results demonstrate that NAA40 affects chromatin dynamics and transcriptional regulation in modulating 20E response, increasing our understanding of the molecular mechanisms underlying the hormonal regulation of gene expression.",

keywords = "ATAC-Seq, And RNA-Seq, Chromatin, Ecdysone",

author = "Arya, \{Surjeet Kumar\} and Palli, \{Subba Reddy\}",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Ltd",

year = "2025",

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doi = "10.1016/j.ibmb.2025.104285",

language = "English",

volume = "179",

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N-alpha-acetyltransferase 40 modulates ecdysteroid action through chromatin accessibility changes near the promoters of 20-hydroxyecdysone response genes in Tribolium Castaneum TcA cells. / Arya, Surjeet Kumar; Palli, Subba Reddy.
In: Insect Biochemistry and Molecular Biology, Vol. 179, 104285, 04.2025.

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

TY - JOUR

T1 - N-alpha-acetyltransferase 40 modulates ecdysteroid action through chromatin accessibility changes near the promoters of 20-hydroxyecdysone response genes in Tribolium Castaneum TcA cells

AU - Arya, Surjeet Kumar

AU - Palli, Subba Reddy

PY - 2025/4

Y1 - 2025/4

N2 - Changes in chromatin accessibility leading to altered gene expression play critical roles in cellular response to environmental signals. The function of N-alpha-acetyltransferase 40 (NAA40) in modulating chromatin accessibility and transcriptional regulation of 20-hydroxyecdysone (20E) response in Tribolium castaneum (TcA) cells was investigated. RNA interference (RNAi) was used to knockdown NAA40, and ATAC and RNA sequencing were used to examine changes in chromatin accessibility and gene expression in TcA cells exposed to 20E. ATAC-seq data revealed chromatin accessibility patterns between NAA40 knockdown and control cells exposed to 20E. Significant differences were detected in chromatin accessibility at transcription start sites (TSS) and promoter regions between dsNAA40 or dsGFP-treated cells exposed to 20E. Differential peak analysis identified many regions in the genome with altered chromatin accessibility upon NAA40 knockdown or 20E treatment, suggesting that NAA40 plays a critical role in 20E regulation of gene expression by modifying chromatin accessibility near the promoters of genes involved in 20E action. RNA sequence data analysis revealed changes in the expression of 20E response genes after NAA40 knockdown or 20E treatment. Comparison of ATAC-seq and RNA-seq data showed a correlation between chromatin accessibility and transcriptional changes of 20E response genes such as E74 and E75. Our results demonstrate that NAA40 affects chromatin dynamics and transcriptional regulation in modulating 20E response, increasing our understanding of the molecular mechanisms underlying the hormonal regulation of gene expression.

AB - Changes in chromatin accessibility leading to altered gene expression play critical roles in cellular response to environmental signals. The function of N-alpha-acetyltransferase 40 (NAA40) in modulating chromatin accessibility and transcriptional regulation of 20-hydroxyecdysone (20E) response in Tribolium castaneum (TcA) cells was investigated. RNA interference (RNAi) was used to knockdown NAA40, and ATAC and RNA sequencing were used to examine changes in chromatin accessibility and gene expression in TcA cells exposed to 20E. ATAC-seq data revealed chromatin accessibility patterns between NAA40 knockdown and control cells exposed to 20E. Significant differences were detected in chromatin accessibility at transcription start sites (TSS) and promoter regions between dsNAA40 or dsGFP-treated cells exposed to 20E. Differential peak analysis identified many regions in the genome with altered chromatin accessibility upon NAA40 knockdown or 20E treatment, suggesting that NAA40 plays a critical role in 20E regulation of gene expression by modifying chromatin accessibility near the promoters of genes involved in 20E action. RNA sequence data analysis revealed changes in the expression of 20E response genes after NAA40 knockdown or 20E treatment. Comparison of ATAC-seq and RNA-seq data showed a correlation between chromatin accessibility and transcriptional changes of 20E response genes such as E74 and E75. Our results demonstrate that NAA40 affects chromatin dynamics and transcriptional regulation in modulating 20E response, increasing our understanding of the molecular mechanisms underlying the hormonal regulation of gene expression.

KW - ATAC-Seq

KW - And RNA-Seq

KW - Chromatin

KW - Ecdysone

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SN - 0965-1748

VL - 179

JO - Insect Biochemistry and Molecular Biology

JF - Insect Biochemistry and Molecular Biology

M1 - 104285

ER -

N-alpha-acetyltransferase 40 modulates ecdysteroid action through chromatin accessibility changes near the promoters of 20-hydroxyecdysone response genes in Tribolium Castaneum TcA cells

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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