Analyzing the relationship of RNA and DNA methylation with gene expression

Abstract Background DNA 5-methylcytosine (5mC) and RNA N6-methyladenosine (m6A) methylation are prevalent modifications in eukaryotes, both playing crucial roles in gene regulation. Recent studies have explored their crosstalk and impact on transcription. However, the intricate relationships among 5...

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Main Authors: Shangqian Xie, Darren Hagen, Gabrielle M. Becker, Kimberly M. Davenport, Katie A. Shira, Morgan R. Stegemiller, Jacob W. Thorne, Sarem Khilji, Denise Konetchy, Patricia Villamediana, Brenda M. Murdoch, Stephanie D. McKay
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Genome Biology
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Online Access:https://doi.org/10.1186/s13059-025-03617-3
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author Shangqian Xie
Darren Hagen
Gabrielle M. Becker
Kimberly M. Davenport
Katie A. Shira
Morgan R. Stegemiller
Jacob W. Thorne
Sarem Khilji
Denise Konetchy
Patricia Villamediana
Brenda M. Murdoch
Stephanie D. McKay
author_facet Shangqian Xie
Darren Hagen
Gabrielle M. Becker
Kimberly M. Davenport
Katie A. Shira
Morgan R. Stegemiller
Jacob W. Thorne
Sarem Khilji
Denise Konetchy
Patricia Villamediana
Brenda M. Murdoch
Stephanie D. McKay
author_sort Shangqian Xie
collection DOAJ
description Abstract Background DNA 5-methylcytosine (5mC) and RNA N6-methyladenosine (m6A) methylation are prevalent modifications in eukaryotes, both playing crucial roles in gene regulation. Recent studies have explored their crosstalk and impact on transcription. However, the intricate relationships among 5mC, m6A, and gene expression remain incompletely elucidated. Results We collect data on 5mC, m6A, and gene expression from samples from three tissues from each of four pregnant cattle and sheep. We construct a comprehensive genome-wide self-interaction (same gene) and across-interaction (across genes) network of 5mC and m6A within gene-bodies or promoters and gene expression in both species. Qualitative analysis identifies uniquely expressed genes with specific m6A methylation in each tissue from both species. A quantitative comparison of gene expression ratio between methylated and unmethylated genes for m6A within gene body and promoter, and 5mC within gene body and promoter confirms the positive effect of RNA methylation on gene expression. Importantly, the influence of RNA methylation on gene expression is stronger than that of DNA methylation. The predominant self- and across-interactions are between RNA methylation within gene bodies and gene expression, as well as between RNA methylation within promoters and gene expression in both species. Conclusions RNA methylation has a stronger effect on gene expression than does DNA methylation within gene bodies and promoters. DNA and RNA methylation in gene-bodies has a greater impact on gene expression than those in promoters. These findings deepen comprehension of the dynamics and complex relationships among the epigenome, epitranscriptome, and transcriptome, offering fresh insights for advancing epigenetics research.
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spelling doaj-art-e631fedfc0784856b68385d3dc183f872025-08-20T02:30:41ZengBMCGenome Biology1474-760X2025-05-0126112410.1186/s13059-025-03617-3Analyzing the relationship of RNA and DNA methylation with gene expressionShangqian Xie0Darren Hagen1Gabrielle M. Becker2Kimberly M. Davenport3Katie A. Shira4Morgan R. Stegemiller5Jacob W. Thorne6Sarem Khilji7Denise Konetchy8Patricia Villamediana9Brenda M. Murdoch10Stephanie D. McKay11Department of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal and Food Sciences, Oklahoma State UniversityDepartment of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal Sciences, Washington State UniversityDepartment of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal, Veterinary and Food Sciences, University of IdahoDepartment of Animal, Veterinary and Food Sciences, University of IdahoDivision of Animal Sciences, University of MissouriAbstract Background DNA 5-methylcytosine (5mC) and RNA N6-methyladenosine (m6A) methylation are prevalent modifications in eukaryotes, both playing crucial roles in gene regulation. Recent studies have explored their crosstalk and impact on transcription. However, the intricate relationships among 5mC, m6A, and gene expression remain incompletely elucidated. Results We collect data on 5mC, m6A, and gene expression from samples from three tissues from each of four pregnant cattle and sheep. We construct a comprehensive genome-wide self-interaction (same gene) and across-interaction (across genes) network of 5mC and m6A within gene-bodies or promoters and gene expression in both species. Qualitative analysis identifies uniquely expressed genes with specific m6A methylation in each tissue from both species. A quantitative comparison of gene expression ratio between methylated and unmethylated genes for m6A within gene body and promoter, and 5mC within gene body and promoter confirms the positive effect of RNA methylation on gene expression. Importantly, the influence of RNA methylation on gene expression is stronger than that of DNA methylation. The predominant self- and across-interactions are between RNA methylation within gene bodies and gene expression, as well as between RNA methylation within promoters and gene expression in both species. Conclusions RNA methylation has a stronger effect on gene expression than does DNA methylation within gene bodies and promoters. DNA and RNA methylation in gene-bodies has a greater impact on gene expression than those in promoters. These findings deepen comprehension of the dynamics and complex relationships among the epigenome, epitranscriptome, and transcriptome, offering fresh insights for advancing epigenetics research.https://doi.org/10.1186/s13059-025-03617-35-methylcytosineN6-methyladenosineMethylationRNA expressionCaruncleCow
spellingShingle Shangqian Xie
Darren Hagen
Gabrielle M. Becker
Kimberly M. Davenport
Katie A. Shira
Morgan R. Stegemiller
Jacob W. Thorne
Sarem Khilji
Denise Konetchy
Patricia Villamediana
Brenda M. Murdoch
Stephanie D. McKay
Analyzing the relationship of RNA and DNA methylation with gene expression
Genome Biology
5-methylcytosine
N6-methyladenosine
Methylation
RNA expression
Caruncle
Cow
title Analyzing the relationship of RNA and DNA methylation with gene expression
title_full Analyzing the relationship of RNA and DNA methylation with gene expression
title_fullStr Analyzing the relationship of RNA and DNA methylation with gene expression
title_full_unstemmed Analyzing the relationship of RNA and DNA methylation with gene expression
title_short Analyzing the relationship of RNA and DNA methylation with gene expression
title_sort analyzing the relationship of rna and dna methylation with gene expression
topic 5-methylcytosine
N6-methyladenosine
Methylation
RNA expression
Caruncle
Cow
url https://doi.org/10.1186/s13059-025-03617-3
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