An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells.
Int J Mol Sci
; 25(1)2023 Dec 28.
Article
in En
| MEDLINE
| ID: mdl-38203607
ABSTRACT
The genome of human adipose-derived stem cells (ADSCs) from abdominal and gluteofemoral adipose tissue depots are maintained in depot-specific stable epigenetic conformations that influence cell-autonomous gene expression patterns and drive unique depot-specific functions. The traditional approach to explore tissue-specific transcriptional regulation has been to correlate differential gene expression to the nearest-neighbor linear-distance regulatory region defined by associated chromatin features including open chromatin status, histone modifications, and DNA methylation. This has provided important information; nonetheless, the approach is limited because of the known organization of eukaryotic chromatin into a topologically constrained three-dimensional network. This network positions distal regulatory elements in spatial proximity with gene promoters which are not predictable based on linear genomic distance. In this work, we capture long-range chromatin interactions using HiChIP to identify remote genomic regions that influence the differential regulation of depot-specific genes in ADSCs isolated from different adipose depots. By integrating these data with RNA-seq results and histone modifications identified by ChIP-seq, we uncovered distal regulatory elements that influence depot-specific gene expression in ADSCs. Interestingly, a subset of the HiChIP-defined chromatin loops also provide previously unknown connections between waist-to-hip ratio GWAS variants with genes that are known to significantly influence ADSC differentiation and adipocyte function.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ascomycota
/
Adipocytes
Limits:
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2023
Type:
Article
Affiliation country:
United States