An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells
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 t...
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| Format: | Article |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/437 |
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| author | Laszlo Halasz Adeline Divoux Katalin Sandor Edina Erdos Bence Daniel Steven R. Smith Timothy F. Osborne |
| author_facet | Laszlo Halasz Adeline Divoux Katalin Sandor Edina Erdos Bence Daniel Steven R. Smith Timothy F. Osborne |
| author_sort | Laszlo Halasz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T15:05:47Z |
| format | Article |
| id | doaj.art-e68b6e50da8a4b759f38e46de30fd0f7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:05:47Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e68b6e50da8a4b759f38e46de30fd0f72024-01-10T14:59:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0125143710.3390/ijms25010437An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem CellsLaszlo Halasz0Adeline Divoux1Katalin Sandor2Edina Erdos3Bence Daniel4Steven R. Smith5Timothy F. Osborne6Division of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USATranslational Research Institute, AdventHealth, Orlando, FL 32804, USADivision of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USADivision of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USADivision of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USATranslational Research Institute, AdventHealth, Orlando, FL 32804, USADivision of Diabetes Endocrinology and Metabolism, Departments of Medicine, Biological Chemistry and Pediatrics, Johns Hopkins University School of Medicine, Institute for Fundamental Biomedical Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL 33701, USAThe 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.https://www.mdpi.com/1422-0067/25/1/437adipose tissueadipose-derived stem celltranscriptomechromatin3D organizationepigenome |
| spellingShingle | Laszlo Halasz Adeline Divoux Katalin Sandor Edina Erdos Bence Daniel Steven R. Smith Timothy F. Osborne An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells International Journal of Molecular Sciences adipose tissue adipose-derived stem cell transcriptome chromatin 3D organization epigenome |
| title | An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells |
| title_full | An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells |
| title_fullStr | An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells |
| title_full_unstemmed | An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells |
| title_short | An Atlas of Promoter Chromatin Modifications and HiChIP Regulatory Interactions in Human Subcutaneous Adipose-Derived Stem Cells |
| title_sort | atlas of promoter chromatin modifications and hichip regulatory interactions in human subcutaneous adipose derived stem cells |
| topic | adipose tissue adipose-derived stem cell transcriptome chromatin 3D organization epigenome |
| url | https://www.mdpi.com/1422-0067/25/1/437 |
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