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Constitutive heterochromatin reorganization during somatic cell reprogramming
Eden Fussner1, Ugljesa Djuric, Mike Strauss
1Programs in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
The EMBO Journal
|April 7, 2011
Summary
Reprogramming induced pluripotent stem (iPS) cells alters heterochromatin structure. Fully reprogrammed iPS cells show dispersed chromatin fibers, unlike compacted heterochromatin in partial iPS cells.
Area of Science:
- Cell Biology
- Epigenetics
- Stem Cell Research
Background:
- Induced pluripotent stem (iPS) cell reprogramming involves epigenetic changes to restore pluripotency.
- While epigenetic marks are reset, the physical ultrastructure of heterochromatin during reprogramming remains unclear.
Purpose of the Study:
- To investigate the physical structure of heterochromatin domains during mouse iPS cell reprogramming.
- To understand how heterochromatin ultrastructure changes from somatic cells to partially reprogrammed and fully reprogrammed iPS cells.
Main Methods:
- Correlative electron spectroscopic imaging was used to analyze heterochromatin structure.
- The study examined heterochromatin in somatic cells, partial iPS cells, and full iPS cells.
Main Results:
- Somatic and partial iPS cells exhibit compartmentalized heterochromatin (H3K9me3-marked) into dense chromocenters.
- Pluripotent stem cells and full iPS cells display poorly defined chromocenter boundaries with dispersed 10 nm heterochromatin fibers.
- Heterochromatin reorganization correlates with retroviral silencing during partial iPS cell reprogramming.
Conclusions:
- Constitutive heterochromatin is compacted in partially reprogrammed iPS cells.
- Acquisition of the fully reprogrammed iPS cell state involves a transition to dispersed 10 nm chromatin fibers.
- Heterochromatin ultrastructure is dynamically remodeled during the epigenetic reprogramming process.
Related Concept Videos
01:32Chromatin Modification in iPS Cells
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...
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...
01:29Somatic to iPS Cell Reprogramming
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 for this...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
02:38Heterochromatin
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at 9th...
03:17Inheritance of Chromatin Structures
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 DNA...
01:24Methods of Nuclear Reprogramming
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 injury repair.