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Somatic to iPS Cell Reprogramming01:29

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
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Related Experiment Video

Updated: Feb 24, 2026

Hemogenic Reprogramming of Human Fibroblasts by Enforced Expression of Transcription Factors
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OCT4 and SOX2 Work as Transcriptional Activators in Reprogramming Human Fibroblasts.

Santosh Narayan1, Gene Bryant1, Shivangi Shah1

  • 1Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Cell Reports
|August 17, 2017
PubMed
Summary
This summary is machine-generated.

SOX2 acts as a transcriptional activator during induced pluripotent stem cell (iPSC) reprogramming. Enhancing SOX2 activation increased reprogramming efficiency, while repression halted it, revealing SOX2

Keywords:
enhancersiPSCsreprogrammingstem cellstranscriptiontranscription factors

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Area of Science:

  • Stem cell biology
  • Epigenetics
  • Molecular biology

Background:

  • The transcription factors SOX2 and OCT4 are crucial for reprogramming somatic cells into induced pluripotent stem cells (iPSCs).
  • Their precise roles as activators or repressors in this process remain incompletely understood.

Purpose of the Study:

  • To elucidate the functional role of SOX2 as a transcriptional activator or repressor during iPSC reprogramming.
  • To investigate the dynamics of DNA-bound transcription factors and enhancer activity during the reprogramming process.

Main Methods:

  • Utilized engineered transcription factor variants, SOX2-VP16 (activator) and SOX2-HP1 (repressor), to replace wild-type SOX2.
  • Analyzed DNA binding of OCT4, SOX2, and SOX2-VP16 at early reprogramming stages.
  • Characterized the formation and strength of putative enhancers associated with these factors.

Main Results:

  • SOX2 functions as a transcriptional activator, similar to OCT4, in iPSC reprogramming.
  • Replacing wild-type SOX2 with SOX2-VP16 enhanced reprogramming efficiency and speed.
  • The SOX2-HP1 repressor variant completely inhibited reprogramming.
  • Early in reprogramming, OCT4, SOX2, and SOX2-VP16 occupied numerous de novo and pre-existing enhancers, with SOX2-VP16 binding to stronger enhancers.
  • Transient enhancer formation and dynamic transcription factor binding were observed during reprogramming.

Conclusions:

  • SOX2's role as a transcriptional activator is critical for efficient iPSC reprogramming.
  • The reprogramming process involves a distinct intermediate state characterized by dynamic enhancer and transcription factor activity.
  • These findings provide insights into the molecular mechanisms governing pluripotency induction.