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Published on: April 21, 2023
Transcription factor-induced enhancer modulations during cell fate conversions
C van Oevelen1, E M Kallin, T Graf
1Gene Regulation, Stem Cells and Cancer Program, Center for Genomic Regulation and Pompeu Fabra University, Barcelona, Spain.
Transcription factors (TFs) drive cell reprogramming into induced pluripotent stem cells (iPSCs) and other cell types. This review explores how TFs access chromatin to alter gene expression and establish new cell identities.
Area of Science:
- * Molecular Biology
- * Developmental Biology
- * Stem Cell Biology
Background:
- * Transcription factors (TFs) are key regulators of gene expression.
- * TFs are essential for cell differentiation, reprogramming into induced pluripotent stem cells (iPSCs), and lineage conversions.
- * Understanding how TFs access and modify chromatin is crucial for controlling these cellular processes.
Purpose of the Study:
- * To discuss the mechanisms by which ectopically expressed TFs access chromatin.
- * To explore how TFs modulate enhancers and establish novel transcriptomes during cellular reprogramming and differentiation.
- * To provide insights into the fundamental questions surrounding TF-mediated gene activation and silencing.
Main Methods:
- * This work is a review, synthesizing existing research and expert knowledge.
- * It focuses on theoretical and mechanistic discussions of TF-chromatin interactions.
- * No new experimental data were generated; it relies on published literature analysis.
Main Results:
- * Ectopically expressed TFs must overcome chromatin barriers to access regulatory elements like enhancers.
- * TFs establish new gene expression programs by altering chromatin accessibility and recruiting necessary enzymes.
- * The process involves both the activation of new genes and the silencing of old ones.
Conclusions:
- * TF-mediated chromatin modulation is central to cell fate plasticity.
- * Further research into TF-chromatin interactions will enhance our ability to control cell reprogramming and differentiation.
- * This understanding is vital for regenerative medicine and developmental biology applications.
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Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...

