Cargando…

Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue

The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the met...

Descripción completa

Detalles Bibliográficos
Autores principales: Vishweswaraiah, Sangeetha, Yilmaz, Ali, Saiyed, Nazia, Khalid, Abdullah, Koladiya, Purvesh R., Pan, Xiaobei, Macias, Shirin, Robinson, Andrew C., Mann, David, Green, Brian D., Kerševičiūte, Ieva, Gordevičius, Juozas, Radhakrishna, Uppala, Graham, Stewart F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530570/
https://www.ncbi.nlm.nih.gov/pubmed/37761892
http://dx.doi.org/10.3390/genes14091752
_version_ 1785111527455457280
author Vishweswaraiah, Sangeetha
Yilmaz, Ali
Saiyed, Nazia
Khalid, Abdullah
Koladiya, Purvesh R.
Pan, Xiaobei
Macias, Shirin
Robinson, Andrew C.
Mann, David
Green, Brian D.
Kerševičiūte, Ieva
Gordevičius, Juozas
Radhakrishna, Uppala
Graham, Stewart F.
author_facet Vishweswaraiah, Sangeetha
Yilmaz, Ali
Saiyed, Nazia
Khalid, Abdullah
Koladiya, Purvesh R.
Pan, Xiaobei
Macias, Shirin
Robinson, Andrew C.
Mann, David
Green, Brian D.
Kerševičiūte, Ieva
Gordevičius, Juozas
Radhakrishna, Uppala
Graham, Stewart F.
author_sort Vishweswaraiah, Sangeetha
collection PubMed
description The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into Huntington’s disease (HD) diagnosis and treatment. Using fourteen post-mortem HD cases and fourteen control subjects, we performed metabolomic profiling of human postmortem brain tissue (striatum and frontal lobe), and we performed DNA methylome profiling using the same frontal lobe tissue. Along with finding several perturbed metabolites and differentially methylated loci, Aminoacyl-tRNA biosynthesis (adj p-value = 0.0098) was the most significantly perturbed metabolic pathway with which two CpGs of the SEPSECS gene were correlated. This study improves our understanding of molecular biomarker connections and, importantly, increases our knowledge of metabolic alterations driving HD progression.
format Online
Article
Text
id pubmed-10530570
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105305702023-09-28 Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue Vishweswaraiah, Sangeetha Yilmaz, Ali Saiyed, Nazia Khalid, Abdullah Koladiya, Purvesh R. Pan, Xiaobei Macias, Shirin Robinson, Andrew C. Mann, David Green, Brian D. Kerševičiūte, Ieva Gordevičius, Juozas Radhakrishna, Uppala Graham, Stewart F. Genes (Basel) Article The impact of environmental factors on epigenetic changes is well established, and cellular function is determined not only by the genome but also by interacting partners such as metabolites. Given the significant impact of metabolism on disease progression, exploring the interaction between the metabolome and epigenome may offer new insights into Huntington’s disease (HD) diagnosis and treatment. Using fourteen post-mortem HD cases and fourteen control subjects, we performed metabolomic profiling of human postmortem brain tissue (striatum and frontal lobe), and we performed DNA methylome profiling using the same frontal lobe tissue. Along with finding several perturbed metabolites and differentially methylated loci, Aminoacyl-tRNA biosynthesis (adj p-value = 0.0098) was the most significantly perturbed metabolic pathway with which two CpGs of the SEPSECS gene were correlated. This study improves our understanding of molecular biomarker connections and, importantly, increases our knowledge of metabolic alterations driving HD progression. MDPI 2023-09-02 /pmc/articles/PMC10530570/ /pubmed/37761892 http://dx.doi.org/10.3390/genes14091752 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vishweswaraiah, Sangeetha
Yilmaz, Ali
Saiyed, Nazia
Khalid, Abdullah
Koladiya, Purvesh R.
Pan, Xiaobei
Macias, Shirin
Robinson, Andrew C.
Mann, David
Green, Brian D.
Kerševičiūte, Ieva
Gordevičius, Juozas
Radhakrishna, Uppala
Graham, Stewart F.
Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue
title Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue
title_full Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue
title_fullStr Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue
title_full_unstemmed Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue
title_short Integrative Analysis Unveils the Correlation of Aminoacyl-tRNA Biosynthesis Metabolites with the Methylation of the SEPSECS Gene in Huntington’s Disease Brain Tissue
title_sort integrative analysis unveils the correlation of aminoacyl-trna biosynthesis metabolites with the methylation of the sepsecs gene in huntington’s disease brain tissue
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530570/
https://www.ncbi.nlm.nih.gov/pubmed/37761892
http://dx.doi.org/10.3390/genes14091752
work_keys_str_mv AT vishweswaraiahsangeetha integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT yilmazali integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT saiyednazia integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT khalidabdullah integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT koladiyapurveshr integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT panxiaobei integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT maciasshirin integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT robinsonandrewc integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT manndavid integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT greenbriand integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT kerseviciuteieva integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT gordeviciusjuozas integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT radhakrishnauppala integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue
AT grahamstewartf integrativeanalysisunveilsthecorrelationofaminoacyltrnabiosynthesismetaboliteswiththemethylationofthesepsecsgeneinhuntingtonsdiseasebraintissue