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Updated: Jun 3, 2025
11:15
Pooled shRNA Screen for Reactivation of MeCP2 on the Inactive X Chromosome
Published on: March 2, 2018
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Single-cell RNA-seq identifies protracted mouse germline X chromosome reactivation dynamics directed by a
Yaqiong Liu1, Xianzhong Lau2, Prabhakaran Munusamy2
1King's College London, Centre for Gene Therapy and Regenerative Medicine, School of Basic & Medical Biosciences, Faculty of Life Sciences and Medicine, London, UK.
Developmental Cell
|January 11, 2025
Summary
Female germ cells reactivate their silenced X chromosome during development. This study tracks X chromosome reactivation (XCR) dynamics, linking it to epigenetic memory and female meiosis.
Area of Science:
- Developmental Biology
- Epigenetics
- Genetics
Background:
- Female primordial germ cells (PGCs) undergo X chromosome reactivation (XCR) during reprogramming.
- The molecular-level kinetics and dynamics of XCR are not well understood.
Purpose of the Study:
- To precisely appraise XCR dynamics in female germ cells from early migratory stages to gonadal development.
- To investigate the temporal link between XCR, germ cell sexual dimorphism, and X chromosome dosage compensation.
- To explore the role of epigenetic memory and Polycomb Repressive Complex 2 (PRC2) in XCR.
Main Methods:
- Single-cell RNA sequencing
- Chromatin profiling
- Allele-specific analysis in F1 mouse embryos
Main Results:
- XCR begins subtly in embryonic day (E)9.5 PGCs and gradually increases, reaching parity by E16.5 oogonia.
- Xist repression occurs from E10.5, but epigenetic memory of X inactivation persists due to PRC2 activity.
- Asymmetric histone H3K27me3 enrichment on the reactivating X chromosome at E13.5 is reversed, enabling germline gene expression.
Conclusions:
- XCR is temporally linked to germ cell sexual dimorphism and dosage compensation.
- Epigenetic memory, maintained by PRC2, influences XCR progression.
- XCR is connected to PRC2 function in promoting female meiosis.
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