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Series GSE256260 Query DataSets for GSE256260
Status Public on May 14, 2024
Title ChIP-seq of active and repressive histone post-translational modifications in human beige and white adipocytes.
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Background: The beneficial effect of thermogenic adipocytes in maintaining body weight and protecting against metabolic disorders has raised interest in understanding the regulatory mechanisms defining white and beige adipocyte identity. Although alternative splicing has been shown to propagate adipose browning signals in mice, this has yet to be thoroughly investigated in human adipocytes. Methods: We performed parallel white and beige adipogenic differentiation using primary adipose stem cells from 6 unrelated healthy subjects, and assessed differential gene and isoform expression in mature adipocytes by RNA sequencing. Results: We find 693 exon junctions with robust differential usage between white and beige adipocytes in all 6 subjects, mapping to 507 genes. Importantly, only 8% of these differentially spliced genes are also differentially expressed, indicating that alternative splicing constitutes an additional layer of gene expression regulation during beige adipocyte adipogenic differentiation. Functional classification of alternative isoforms point to a gain of function for key thermogenic regulators such as PPARG, CITED1 and PEMT. We find that a large majority of the splice variants arise from differential usage of transcription start sites (TSSs), with beige-specific TSSs being enriched for PPARĪ³ and MED1 binding compared to white-specific TSSs. Finally, we validate beige specific isoform expression at the protein level for two thermogenic regulators, PPARĪ³ and PEMT. Discussion: These results indicate that differential isoform expression through alternative TSS usage is an important regulatory mechanism for human adipocyte thermogenic specification.
 
Overall design Primary human adipocyte stem cells from a single subject were differentiated into both beige and white adipocytes in the presence or absence of rosiglitazone, respectively, and harvested for Chromatin Immunoprecipation and sequencing (ChIP-Seq). Four histone post translational modifications were assayed: H3K4me3, H3K27ac, H3K4me1 and H3K27me3.
 
Contributor(s) Hazell Pickering S, Abdelhalim M, Collas P, Briand N
Citation Sarah Hazell Pickering, Mohamed Abdelhalim, Philippe Collas, and Nolwenn Briand. Alternative isoform expression of key thermogenic genes in human beige adipocytes. Front Endocrinol, Vol 15, 2024. doi:10.3389/fendo.2024.1395750
Submission date Feb 21, 2024
Last update date Jun 05, 2024
Contact name Philippe Collas
Organization name University of Oslo
Department Institute of Basic Medical Sciences
Street address PO Box 1112 Blindern
City Oslo
ZIP/Postal code 0317
Country Norway
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (10)
GSM8092134 white_H3K4me3_ChIP
GSM8092135 beige_H3K4me3_ChIP
GSM8092136 white_H3K27me3_ChIP
This SubSeries is part of SuperSeries:
GSE256262 Alternative isoform expression of key thermogenic genes in human beige adipocytes
Relations
BioProject PRJNA1078804

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Supplementary file Size Download File type/resource
GSE256260_RAW.tar 7.4 Gb (http)(custom) TAR (of BROADPEAK, BW, NARROWPEAK)
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Raw data are available in SRA

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