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Genome-wide Snapshot of Chromatin Regulators and States in Xenopus Embryos by ChIP-Seq
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A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819
Liane P Fernandes1, Rocio Enriquez-Gasca1, Poppy A Gould1
1Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London E1 2AT, UK.
Science Advances
|October 28, 2022
Summary
KRAB-zinc finger proteins (KZFPs) regulate cell fate. ZFP819 depletion in mouse stem cells activates totipotency genes by altering DNA, promoting a 2-cell-like state and hindering differentiation.
Area of Science:
- Genomics
- Epigenetics
- Developmental Biology
Background:
- Mammalian genomes exhibit genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs).
- KZFPs play a role in regulating genome stability and gene expression.
- Satellite DNA arrays are known to interact with KZFPs.
Purpose of the Study:
- To investigate the role of ZFP819, a KRAB-zinc finger protein, in regulating cell fate.
- To determine how ZFP819 interacts with the ZP3AR satellite DNA array.
- To understand the impact of ZFP819 depletion on mouse embryonic stem cell (mESC) state and differentiation.
Main Methods:
- Depletion of ZFP819 in mouse embryonic stem cells (mESCs).
- Analysis of ZP3AR satellite DNA array state (poised vs. active enhancer).
- Assessment of heterochromatin changes, SETDB1 stability, and LINE-1 element transcription.
Main Results:
- ZFP819 depletion induced a transition to a 2-cell (2C)-like state in mESCs.
- The ZP3AR array switched from a poised to an active enhancer state upon ZFP819 depletion.
- Global heterochromatin erosion and decreased SETDB1 stability were observed, leading to LINE-1 activation and impaired differentiation.
Conclusions:
- ZFP819 and TRIM28 collaborate to repress chromatin at the Zscan4 locus, facilitating exit from totipotency.
- Satellite DNA arrays may function as regulators of developmental fate transitions by silencing master transcription factors.
- This study reveals a novel mechanism by which KZFPs and satellite DNA control cell identity.
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