Abstract: SA-PO636
Chromatin Conformation and Histone Modification Profiling across Human Kidney Anatomic Regions
Session Information
- Genetic Kidney Diseases: Models, Mechanisms, and Therapies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Li, Dian, Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
- Li, Haikuo, Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
- Isnard, Pierre, Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
- Humphreys, Benjamin D., Division of Nephrology, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, United States
Background
Delineating human kidney anatomical structures using high-throughput transcriptomic methodologies has provided a deeper understanding of region-specific function and pathophysiology. Less is known concerning epigenetic mechanisms, such as 3D chromatin architecture and histone modification and how this changes in different kidney cell types and regions.
Methods
We leveraged our recently developed high-yield nuclei extraction method to simultaneously profile chromatin conformation capture with Hi-C and H3K4me3/H3K27 histone modification with Cleavage Under Targets and Release Using Nuclease (CUT&RUN) sequencing samples of human kidney cortex, medulla, and papilla dissected from a healthy donor. We also performed inter-study comparisons of 3 previously published CUT&RUN datasets.
Results
We generated 6 Hi-C and 18 CUT&RUN libraries, at an average depth of 578 million and 19 million reads. We built Hi-C chromatin contact maps for each kidney region at a resolution of 5,000 bp and inter-region difference maps. We observed that long-cis interactions (>20 kb apart), accounted for >50% of the contact events. Interestingly, we identified region-specific contact enrichments along with their marker genes (RUNX1, Fig. 1A). Regarding CUT&RUN, we detected that over 75% of H3K4me3 (enhancer) peaks were localized to the promoter regions, and 34% to 51% of H3K27me3 (repressor) peaks over distal intergenic regions. Similarly, we identified variations in peak abundances across different kidney regions, with the medulla accounting for the fewest peaks for both histone modifications (Fig. 1B).
Conclusion
We describe a comprehensive epigenetic landscape across human kidney anatomical regions. Importantly, we identified region-specific epigenetic modifications which further emphasizes at a molecular level the importance of segment-specific differentiation of the human kidney.
Funding
- NIDDK Support