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| Status |
Public on Feb 11, 2024 |
| Title |
Nuclear Morphology is Instructed by the Loop Extrusion Program [HiC] |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
More than a century ago Metchnikoff defined neutrophils as small amoeboid-like cells that harbored peculiar polymorphonuclear structures. While since these early studies much has been learned about neutrophil physiology, mechanistic insight into neutrophil polymorphonuclear assembly remains rudimentary. Here we found that depletion of factors, that initiate the loop extrusion program, including NIPBL and MAU2, greatly accelerated the conversion of mononuclear to polymorphonuclear cells and orchestrated the induction of a neutrophil specific transcription signature. Remarkably, mere ablation of either NIPBL or MAU2 expression under conditions that normally prevent neutrophil differentiation, swiftly converted mono-nuclear into polymorphonuclear cells that expressed a neutrophil specific gene program. Depletion of NIPBL and MAU2 in neutrophil progenitors activated an armamentarium of neutrophil-specific enhancers to establish a neutrophil genome depleted for loop extrusion-induced looping. These observations indicate that extinction of the loop extrusion program converts mononuclear progenitor cells into polymorphonuclear cells and suffices to induce a neutrophil specific program of gene expression.
Expression profiling by high throughput sequencing
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| Overall design |
Hi-C was performed using two independent replicates of NIPBL-FKBP12F36V-EYFP progenitor cells that were cultured in the presence of β-estradiol and in the presence or absence of dTAG-13 for 72hrs
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| Contributor(s) |
Patta I, Hu M, Murre C |
| Citation(s) |
38355805 |
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| Submission date |
May 09, 2023 |
| Last update date |
Mar 14, 2024 |
| Contact name |
Indumathi Patta |
| Organization name |
UCSD
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| Department |
Molecular Biology
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| Lab |
Cornelis Murre Lab
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| Street address |
9500 Gilman Drive, NSB5114A, LaJolla
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| City |
SAN DIEGO |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| GSM7311305 |
NIPBL Untreated +estradiol 72hrs replicate1 Hi-C |
| GSM7311306 |
NIPBL Untreated +estradiol 72hrs replicate2 Hi-C |
| GSM7311307 |
NIPBL dTAG treated +estradiol 72hrs replicate1 Hi-C |
| GSM7311308 |
NIPBL dTAG treated +estradiol 72hrs replicate2 Hi-C |
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| Relations |
| BioProject |
PRJNA970727 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232064_RAW.tar |
1.8 Gb |
(http)(custom) |
TAR (of HIC) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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