An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes

Vitamin B12 has multiple biochemical functions including in the one-carbon cycle generating a methyl group for DNA methylation, and metabolism of fatty acids and amino acids to generate energy via the citric acid cycle. The aim of our study was to use a combined epigenomic and transcriptomic approac...

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Main Authors: B. William Ogunkolade, Antonysunil Adaikalakoteswari, Shirleny Romualdo Cardoso, Rob Lowe, Nisha Patel, Vardhman Rakyan, Sarah Finer, Martin Wabitsch, Ponnusamy Saravanan, Gyanendra Tripathi, Elena Bochukova, Graham A Hitman
Format: Article
Language:English
Published: Taylor & Francis Group 2022-10-01
Series:Epigenetics
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Online Access:http://dx.doi.org/10.1080/15592294.2021.2003043
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author B. William Ogunkolade
Antonysunil Adaikalakoteswari
Shirleny Romualdo Cardoso
Rob Lowe
Nisha Patel
Vardhman Rakyan
Sarah Finer
Martin Wabitsch
Ponnusamy Saravanan
Gyanendra Tripathi
Elena Bochukova
Graham A Hitman
author_facet B. William Ogunkolade
Antonysunil Adaikalakoteswari
Shirleny Romualdo Cardoso
Rob Lowe
Nisha Patel
Vardhman Rakyan
Sarah Finer
Martin Wabitsch
Ponnusamy Saravanan
Gyanendra Tripathi
Elena Bochukova
Graham A Hitman
author_sort B. William Ogunkolade
collection DOAJ
description Vitamin B12 has multiple biochemical functions including in the one-carbon cycle generating a methyl group for DNA methylation, and metabolism of fatty acids and amino acids to generate energy via the citric acid cycle. The aim of our study was to use a combined epigenomic and transcriptomic approach to identify novel genes mediating the effect of B12 on adipogenesis. Human pre-adipocytes (CHUB-S7) were treated with a range of B12 (0–500 nM) concentrations from the day of cell seeding until harvesting in discovery and validation experiments prior to genome-wide methylation analysis using the Illumina HumanMethylation 450Beadchip. For transcriptomic analysis, RNA-seq libraries were run on the Illumina HiSeq 2500. To further investigate the expression of any genes on human adipogenesis, a second human preadipocyte strain was studied (SGBS) by real-time quantitative PCR (qRT-PCR). A combined epigenetic and transcriptomic approach in differentiated human pre-adipocyte cell line, CHUB-S7, identified that the Human cartilage chitinase 3-like protein 2 (CHI3L2) gene was hypo-methylated and had increased expression in low B12 conditions. Furthermore, there was an approximately 1000-fold increase in CHI3L2 expression in the early days of adipocyte differentiation, which paralleled an increase of lipid droplets in differentiated SGBS cells and an increased expression level of markers of mature adipocytes. In summary, we have identified a potential role of the human cartilage chitinase 3-like protein 2 (CHI3L2) in adipocyte function in the presence of low B12 levels.
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spelling doaj.art-da875f7227f04099ad63049ddd7f39342023-09-21T13:23:11ZengTaylor & Francis GroupEpigenetics1559-22941559-23082022-10-0117101219123310.1080/15592294.2021.20030432003043An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytesB. William Ogunkolade0Antonysunil Adaikalakoteswari1Shirleny Romualdo Cardoso2Rob Lowe3Nisha Patel4Vardhman Rakyan5Sarah Finer6Martin Wabitsch7Ponnusamy Saravanan8Gyanendra Tripathi9Elena Bochukova10Graham A Hitman11Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonWarwick Medical School, University of WarwickBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonUlm University HospitalWarwick Medical School, University of WarwickWarwick Medical School, University of WarwickBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonBlizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of LondonVitamin B12 has multiple biochemical functions including in the one-carbon cycle generating a methyl group for DNA methylation, and metabolism of fatty acids and amino acids to generate energy via the citric acid cycle. The aim of our study was to use a combined epigenomic and transcriptomic approach to identify novel genes mediating the effect of B12 on adipogenesis. Human pre-adipocytes (CHUB-S7) were treated with a range of B12 (0–500 nM) concentrations from the day of cell seeding until harvesting in discovery and validation experiments prior to genome-wide methylation analysis using the Illumina HumanMethylation 450Beadchip. For transcriptomic analysis, RNA-seq libraries were run on the Illumina HiSeq 2500. To further investigate the expression of any genes on human adipogenesis, a second human preadipocyte strain was studied (SGBS) by real-time quantitative PCR (qRT-PCR). A combined epigenetic and transcriptomic approach in differentiated human pre-adipocyte cell line, CHUB-S7, identified that the Human cartilage chitinase 3-like protein 2 (CHI3L2) gene was hypo-methylated and had increased expression in low B12 conditions. Furthermore, there was an approximately 1000-fold increase in CHI3L2 expression in the early days of adipocyte differentiation, which paralleled an increase of lipid droplets in differentiated SGBS cells and an increased expression level of markers of mature adipocytes. In summary, we have identified a potential role of the human cartilage chitinase 3-like protein 2 (CHI3L2) in adipocyte function in the presence of low B12 levels.http://dx.doi.org/10.1080/15592294.2021.2003043vitamin b12adipocyteepigenometranscriptomechi3l2
spellingShingle B. William Ogunkolade
Antonysunil Adaikalakoteswari
Shirleny Romualdo Cardoso
Rob Lowe
Nisha Patel
Vardhman Rakyan
Sarah Finer
Martin Wabitsch
Ponnusamy Saravanan
Gyanendra Tripathi
Elena Bochukova
Graham A Hitman
An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes
Epigenetics
vitamin b12
adipocyte
epigenome
transcriptome
chi3l2
title An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes
title_full An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes
title_fullStr An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes
title_full_unstemmed An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes
title_short An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 (CHI3L2) as a potential mediator of B12 deficiency in adipocytes
title_sort integrative epi transcriptomic approach identifies the human cartilage chitinase 3 like protein 2 chi3l2 as a potential mediator of b12 deficiency in adipocytes
topic vitamin b12
adipocyte
epigenome
transcriptome
chi3l2
url http://dx.doi.org/10.1080/15592294.2021.2003043
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