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Histone variant macroH2A confers resistance to nuclear reprogramming
Vincent Pasque1, Astrid Gillich, Nigel Garrett
1Wellcome Trust Cancer Research UK Gurdon Institute, Cambridge, UK. v.pasque@gurdon.cam.ac.uk
The EMBO Journal
|May 10, 2011
Summary
The inactive X chromosome (Xi) in mouse epiblast stem cells is reprogrammable, unlike in differentiated cells. MacroH2A histone variant incorporation limits epigenetic reprogramming by oocytes.
Area of Science:
- Epigenetics
- Developmental Biology
- Cell Biology
Background:
- Somatic cell nuclear reprogramming is crucial for understanding gene regulation.
- The inactive X chromosome (Xi) presents a barrier to reprogramming.
- Mechanisms restricting Xi reprogramming remain unclear.
Purpose of the Study:
- Investigate epigenetic factors limiting somatic cell nuclear reprogramming.
- Assess the stability of the inactive X chromosome (Xi) during reprogramming.
- Identify key epigenetic marks associated with Xi reversibility.
Main Methods:
- Nuclear transfer of mammalian somatic cell nuclei into Xenopus oocytes.
- Analysis of inactive X chromosome (Xi) stability in different cell types.
- Assessment of epigenetic marks including DNA methylation, H3K27me3, and macroH2A.
Main Results:
- The Xi in epiblast stem cells (EpiSCs) is reversible by nuclear transfer, while in differentiated/extraembryonic cells, it is irreversible.
- Xist RNA is lost from the Xi after nuclear transfer.
- DNA methylation and H3K27me3 do not fully explain Xi reversibility differences.
- MacroH2A histone variant incorporation correlates with Xi resistance to reprogramming.
Conclusions:
- Epiblast stem cell Xi exhibits decreased stability, allowing reprogramming.
- MacroH2A incorporation into the Xi is a key epigenetic barrier to oocyte-mediated reprogramming.
- Combinatorial epigenetic repression involving macroH2A restricts transcriptional reprogramming.
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