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Updated: Dec 26, 2025
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Epigenetic activation of the 5-hydroxytryptamine (serotonin) receptor 2C in embryonal carcinoma cells is DNA
Daria L Bancescu1, Heather Glatt-Deeley, Marc Lalande
1Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington 06030-3301, USA.
Abstract:
The epigenetic states of key regulatory genes must be altered to drive cell fate decisions in differentiating cells. This process must be coupled, at least transiently, to the DNA replication machinery. Only a few genes, however, have been shown to require DNA replication for their activation or repression upon induction of differentiation. We have developed a methodology for examining how gene expression is coupled to cell division during the early stages of differentiation of embryonal carcinoma (EC) cells. Using this approach, we find that the expression of the 5-hydroxytryptamine (serotonin) receptor 2C (Htr2c) is strongly increased in the second division after all-trans retinoic acid addition. We propose that the epigenetic activation of Htr2c in EC cells results from a chromatin remodeling process that requires at least two passages through S phase.
Insights
Cell differentiation requires epigenetic changes linked to DNA replication. This study reveals serotonin receptor 2C (Htr2c) gene activation during embryonal carcinoma cell differentiation necessitates two cell divisions for epigenetic remodeling.
Area of Science:
- Epigenetics
- Developmental Biology
- Molecular Biology
Background:
- Cell fate decisions during differentiation involve dynamic epigenetic alterations.
- Gene expression changes are often coupled to DNA replication during cell division.
- Few specific genes have been identified that require DNA replication for epigenetic modulation during differentiation.
Purpose of the Study:
- To develop a methodology for studying gene expression coupled to cell division in early differentiation.
- To investigate the epigenetic regulation of gene expression during embryonal carcinoma (EC) cell differentiation.
- To identify genes whose epigenetic activation is dependent on DNA replication.
Main Methods:
- Developed a novel methodology to track gene expression relative to cell division stages.
- Utilized embryonal carcinoma (EC) cells induced to differentiate with all-trans retinoic acid.
- Quantified gene expression changes across successive cell cycles post-induction.
Main Results:
- Identified the 5-hydroxytryptamine (serotonin) receptor 2C (Htr2c) gene as significantly upregulated.
- Observed a strong increase in Htr2c expression specifically in the second cell division after differentiation induction.
- Demonstrated a correlation between Htr2c epigenetic activation and passage through S phase.
Conclusions:
- Epigenetic activation of Htr2c during EC cell differentiation is intrinsically linked to the cell cycle.
- Chromatin remodeling leading to Htr2c activation requires at least two DNA replication cycles (S phases).
- This finding highlights a specific mechanism where gene activation is coupled to cell division during early differentiation.
