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Identification of Enhancer-Promoter Contacts in Embryoid Bodies by Quantitative Chromosome Conformation Capture (4C)
Published on: April 29, 2020
Identification of an ES cell pluripotent state-specific DUSP6 enhancer
Jiaxing Zhang1, Jun Nomura, Masayoshi Maruyama
1Division of Developmental Biology, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241, Japan.
Researchers identified a novel regulatory element, PEDRE, controlling dual specificity phosphatase 6 (DUSP6) expression in embryonic stem (ES) cells. This finding highlights conserved gene regulation crucial for maintaining pluripotency.
Area of Science:
- Stem cell biology
- Molecular genetics
- Gene regulation
Background:
- Embryonic stem (ES) cells possess pluripotency, the ability to differentiate into various cell types.
- Identifying genes with pluripotent state-specific expression is crucial for understanding stem cell biology.
- Dual specificity phosphatase 6 (DUSP6) is known to be expressed in undifferentiated human ES cells.
Purpose of the Study:
- To identify genes specifically expressed in the pluripotent state of mouse embryonic stem (ES) cells.
- To characterize the regulatory elements controlling the pluripotent state-specific expression of DUSP6.
Main Methods:
- Comparative gene expression profiling of undifferentiated and differentiated mouse ES cells using DNA microarrays.
- Identification and characterization of a novel regulatory enhancer (PEDRE) for DUSP6.
- Sequence comparison of PEDRE between mouse and human DUSP6.
Main Results:
- DNA microarrays identified numerous genes with pluripotent state-specific expression.
- Dual specificity phosphatase 6 (DUSP6) was identified as a key gene of interest.
- A novel 82-base pair regulatory enhancer, termed PEDRE, was identified and characterized.
- PEDRE controls the pluripotent state-specific expression of DUSP6.
- PEDRE is distinct from, but overlaps with, a previously identified FGF-ERK pathway-regulated element.
- PEDRE sequence is 100% identical between mouse and human DUSP6.
Conclusions:
- A novel enhancer, PEDRE, regulates DUSP6 expression in a pluripotent state-specific manner.
- The molecular basis for DUSP6 gene expression in undifferentiated ES cells is highly conserved between mouse and human.
- This conserved regulation suggests a fundamental role in maintaining pluripotency.
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