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Published on: May 30, 2012
Global transcription in pluripotent embryonic stem cells
Sol Efroni1, Radharani Duttagupta, Jill Cheng
1National Cancer Institute Center for Bioinformatics, National Institutes of Health, Rockville, MD 20852, USA.
Embryonic stem cells (ESCs) exhibit global transcriptional hyperactivity, with active repeat regions and widespread gene expression. As cells differentiate, this activity reduces, leading to large-scale silencing and discrete transcriptional landscapes, driving lineage specification.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Genomics
Background:
- Molecular mechanisms of pluripotency and lineage specification in embryonic stem cells (ESCs) remain poorly understood.
- Differentiation may involve targeted gene activation or selective silencing of genomic regions.
Purpose of the Study:
- To investigate the global transcriptional state of ESCs and its changes during differentiation.
- To elucidate the role of widespread transcription in maintaining pluripotency and driving lineage commitment.
Main Methods:
- Utilized whole-genome tiling arrays to analyze transcription across coding and noncoding regions.
- Compared transcriptional landscapes of pluripotent ESCs with differentiating cells.
Main Results:
- ESCs display globally hyperactive transcription, including active normally silent repeat regions and low-level expression of tissue-specific genes.
- Differentiation leads to large-scale silencing and a more discrete transcriptional landscape.
- Transcriptional hyperactivity in ESCs correlates with increased expression of chromatin-remodeling and general transcription machinery genes.
Conclusions:
- Global transcription is a key characteristic of pluripotent ESCs, supporting their plasticity.
- Lineage specification is driven by a reduction in the actively transcribed portion of the genome.
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