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Updated: Aug 13, 2025
08:27
A Non-random Mouse Model for Pharmacological Reactivation of Mecp2 on the Inactive X Chromosome
Published on: May 22, 2019
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Cohesin controls X chromosome structure remodeling and X-reactivation during mouse iPSC-reprogramming
Serena F Generoso1, Maria Victoria Neguembor1, Elliot A Hershberg2
1Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona 08003, Spain.
Summary
Cohesin, specifically SMC1a, is crucial for reactivating the inactive X chromosome during induced pluripotent stem cell (iPSC) reprogramming. This epigenetic remodeling is essential for X chromosome reactivation (XCR) and pluripotency.
Area of Science:
- Epigenetics
- Chromatin Biology
- Stem Cell Biology
Background:
- X chromosome reactivation (XCR) is vital for pluripotency in female cells.
- The molecular mechanisms governing XCR during induced pluripotent stem cell (iPSC) reprogramming remain poorly understood.
Purpose of the Study:
- To identify molecular factors involved in XCR during iPSC reprogramming.
- To elucidate the role of SMC1a in X chromosome structure and function.
Main Methods:
- RNAi-based knockdown screen in mouse fibroblasts during iPSC reprogramming.
- Super-resolution microscopy to assess SMC1a localization and X chromosome structure.
Main Results:
- Identified SMC1a, a cohesin complex member, as critical for XCR.
- SMC1a is enriched on the active X chromosome and maintains its decompacted state.
- SMC1a depletion compacts the active X chromosome without hindering iPSC reprogramming.
Conclusions:
- Cohesin, particularly SMC1a, plays a key role in remodeling the inactive X chromosome to an active state.
- SMC1a is essential for X chromosome reactivation during the iPSC reprogramming process.
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