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Chromatin Modification in iPS Cells01:32

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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...
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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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Nuclear reprogramming is a process of transforming one cell type into an unrelated cell type by epigenetic changes that alter the cell’s original gene expression pattern. Such epigenetic changes force cells to express a different set of genes, which play a significant role in inducing transformation into other cell types. Nuclear reprogramming offers applications in reproductive cloning for livestock propagation and regenerative medicine — developing patient-specific cells for...
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
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Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
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Chromatin Accessibility Dynamics during iPSC Reprogramming.

Dongwei Li1, Jing Liu2, Xuejie Yang1

  • 1CAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Cell Stem Cell
|December 9, 2017
PubMed
Summary
This summary is machine-generated.

Cell reprogramming involves dynamic chromatin changes. Key factors like Sap30 regulate chromatin accessibility, influencing cell fate decisions and pluripotency.

Keywords:
Sap30binary logicchromatin dynamicsopen/closereprogramming

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Stem Cell Biology

Background:

  • Cell-fate decisions are fundamental to development and disease.
  • Understanding chromatin dynamics during cell reprogramming is crucial.
  • Current knowledge of chromatin remodeling during induced pluripotency is limited.

Purpose of the Study:

  • To map dynamic chromatin remodeling during induced pluripotent stem cell (iPSC) generation.
  • To investigate the role of specific transcription factors and epigenetic modifiers in these dynamics.
  • To elucidate the chromatin accessibility logic governing cell-fate transitions.

Main Methods:

  • Performed ATAC-seq profiling on mouse embryonic fibroblasts (MEFs) expressing reprogramming factors Oct4-Sox2-Klf4 (OSK).
  • Analyzed dynamic shifts between open (OC) and closed (CO) chromatin states.
  • Investigated the enrichment of transcription factor motifs and histone modifications (H3K27ac).
  • Assessed the impact of reprogramming inhibitors and the role of Sap30.

Main Results:

  • Observed dynamic chromatin state transitions (OC and CO) during OSK-induced reprogramming.
  • Identified OC loci associated with somatic genes and CO loci with pluripotency genes.
  • Found that reprogramming impediments disrupt normal OC-CO dynamics.
  • Demonstrated that OSK motifs enrich CO loci, while OC loci suggest alternative closing mechanisms.
  • Showed Sap30 is essential for the OC shift and H3K27ac reduction at OC loci.

Conclusions:

  • Reprogramming follows a specific chromatin accessibility logic involving dynamic OC and CO states.
  • Sap30 and epigenetic modifications play critical roles in regulating chromatin accessibility during cell-fate decisions.
  • These findings provide insights into the epigenetic mechanisms underlying cell plasticity and may extend to other cell-fate transitions.