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| Status |
Public on Oct 07, 2024 |
| Title |
Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation [Hi-C] |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
The organization of the genome in three-dimensional space is highly dynamic, yet how these dynamics are regulated and the role they play in genome function is poorly understood. Here, we utilized acute depletion of NIPBL to characterize the role of cohesin-mediated loop extrusion in vivo. Using this approach, we find that many chromatin loops are rapidly diminished upon loss of NIBPL, consistent with recent single locus imaging studies showing that chromatin loops are transient. However, we also identified a subset of cohesin-dependent chromatin loops that are anchored in repressive chromatin and may be “long-lived”, given that they require NIPBL for their establishment upon mitotic exit, but are persistent when NIPBL is depleted from interphase cells. In addition to the reformation of 3D genome structures, mitotic exit coincides with widespread transcriptional activation. We found that NIPBL is essential for establishing the expression of lineage-defining genes during the M-G1 transition but has diminished impact in the steady-state maintenance of their expression. At genes sensitive to its depletion, NIPBL supports a unique local genome organization defined by greater spatial proximity to nearby enhancers and weaker transcription start site insulation of genomic contacts. Overall, we show that NIPBL-mediated loop extrusion is critical to genome organization and transcriptional regulation in vivo.
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| |
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| Overall design |
Role of NIPBL in post-mitotic transcriptional reactivation, chromatin association of cohesin, and 3D genome organization.
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| Contributor(s) |
Popay TM, Dixon JR |
| Citation missing |
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| |
| Submission date |
Sep 21, 2024 |
| Last update date |
Oct 08, 2024 |
| Contact name |
Jesse R Dixon |
| E-mail(s) |
jedixon@salk.edu
|
| Organization name |
Salk Institute for Biological Studies
|
| Lab |
PBL-D
|
| Street address |
10010 N. Torrey Pines Rd.
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL34281 |
Illumina NovaSeq X (Homo sapiens) |
|
| Samples (36)
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| This SubSeries is part of SuperSeries: |
| GSE277721 |
Genome-wide in vivo dynamics of cohesin-mediated loop extrusion and its role in transcription activation |
|
| Relations |
| BioProject |
PRJNA1163538 |
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