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Multiscale 3D genome rewiring during PTF1A-mediated somatic cell reprogramming into neural stem cells
Rong Zhang1, Jun Sun2,3,4,5, Shuting Liu1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, China.
Communications Biology
|November 13, 2024
Summary
The transcription factor PTF1A reprograms the 3D genome during cell fate transitions. It reorganizes chromatin loops and gene expression to drive fibroblast transdifferentiation into neural stem cells (NSCs).
Area of Science:
- Genomics
- Epigenetics
- Cell Biology
Background:
- The genome's higher-order organization into compartments, TADs, and loops is cell-type specific.
- The role of 3D genome organization in regulating cell fate transitions is not fully understood.
Purpose of the Study:
- To investigate how PTF1A orchestrates 3D genome remodeling during fibroblast to NSC transdifferentiation.
- To elucidate the mechanisms by which PTF1A controls gene expression and cell fate during reprogramming.
Main Methods:
- Multiomics analyses integrating Hi-C, DNA-binding profiles (PTF1A, CTCF), H3K27ac modification, and gene expression data.
- Analysis of PTF1A binding sites, CTCF occupancy, and enhancer activity during transdifferentiation.
Main Results:
- PTF1A binds to subTAD boundaries, increasing CTCF binding and boundary insulation.
- PTF1A reorganizes chromatin loops, altering gene expression to drive NSC differentiation.
- PTF1A activates enhancers and modulates H3K27ac deposition, promoting cell fate changes.
Conclusions:
- PTF1A plays a crucial role in controlling gene expression and remodeling the 3D genome during cell reprogramming.
- 3D genome organization is implicated in transcriptional and cell fate alterations during cell reprogramming.
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