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| Status |
Public on Jul 12, 2023 |
| Title |
Epigenetic and transcriptomic alterations in key inflammatory pathways are established in RUNX1 deficient hematopoietic progenitors and are propagated to neutrophils [Human ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Epigenome and transcriptome characterization of RUNX1 deficient hematopoietic cells. We hypothesized that epigenetic alterations in key inflammatory pathway genes are acquired in RUNX1 deficient granulocyte-monocyte progenitors (GMPs) and are propagated to neutrophils. We deleted RUNX1 using Cebpa-Cre, which deletes primarily in GMPs. We analyzed the basal transcriptional changes caused by the loss of RUNX1 in purified GMPs and neutrophils by bulk RNA-seq. We evaluated if the loss of RUNX1 leads to changes in chromatin accessibility in GMPs and neutrophils by ATAC-seq. We determined that there was increased chromatin accessibility of transposable elements (TEs) in RUNX1 deficient cells. To determine if we could detect dsRNA from TEs, we pulled down dsRNA using the 9D5 antibody and performed RNA-seq. To gain insight into how RUNX1 loss affects active enhancers, we performed H3K27ac ChIP-seq on control and Runx1 deficient neutrophils. We also evaluated if RUNX1 mutations in patient neutrophils lead to changes in chromatin accessibility by ATAC-seq. We then performed Hi-C to evaluate the global high-order chromatin organization in GMPs and neutrophils. Finally, we performed RUNX1 CUT&RUN to determine RUNX1 occupancy sites in GMPs.
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| Overall design |
Examination of transcriptome, chromatin accessibility, and histone modifications in RUNX1 mouse deficient GMPs and neutrophils, and patient neutrophils.
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| Contributor(s) |
Zezulin AU, Howell ED, Ye D, Tan K, Yu W, Speck NA |
| Citation(s) |
37536952 |
| |
| Submission date |
Dec 20, 2022 |
| Last update date |
Aug 07, 2023 |
| Contact name |
Alexandra Zezulin |
| E-mail(s) |
Alexandra.zezulin@pennmedicine.upenn.edu
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| Organization name |
University of Pennsylvania
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| Lab |
Speck Lab
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| Street address |
421 Curie Blvd 544 BRB II/III
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| City |
Philadelphia |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE221427 |
Epigenetic and transcriptomic alterations in key inflammatory pathways are established in RUNX1 deficient hematopoietic progenitors and are propagated to neutrophils. |
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| Relations |
| BioProject |
PRJNA914284 |
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