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

Ogunkolade, BW, Adaikalakoteswari, A ORCID: https://orcid.org/0000-0003-2974-3388, Cardoso, SR, Lowe, R, Patel, N, Rakyan, V, Finer, S, Wabitsch, M, Saravanan, P, Tripathi, G, Bochukova, E and Hitman, GA, 2021. 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. ISSN 1559-2294

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Abstract

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.

Item Type:	Journal article
Publication Title:	Epigenetics
Creators:	Ogunkolade, B.W., Adaikalakoteswari, A., Cardoso, S.R., Lowe, R., Patel, N., Rakyan, V., Finer, S., Wabitsch, M., Saravanan, P., Tripathi, G., Bochukova, E. and Hitman, G.A.
Publisher:	Taylor & Francis
Date:	25 November 2021
ISSN:	1559-2294
Identifiers:	Number Type 10.1080/15592294.2021.2003043 DOI 1500086 Other
Rights:	© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-ncnd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	01 Dec 2021 10:33
Last Modified:	01 Dec 2021 10:33
URI:	https://irep.ntu.ac.uk/id/eprint/45018

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