Programmable genetic switches to control transcriptional machinery of pluripotency

@article{Pandian2012ProgrammableGS,
  title={Programmable genetic switches to control transcriptional machinery of pluripotency},
  author={Ganesh Namasivayam Pandian and Hiroshi Sugiyama},
  journal={Biotechnology Journal},
  year={2012},
  volume={7}
}
Transcriptional activators play a central role in the regulation of gene expression and have the ability to manipulate the specification of cell fate. Pluripotency is a transient state where a cell has the potential to develop into more than one type of mature cell. The induction of pluripotency in differentiated cells requires extensive chromatin reorganization regulated by core transcriptional machinery. Several small molecules have been shown to enhance the efficiency of somatic cell… 
View on Wiley
ncbi.nlm.nih.gov
35 Citations
Background Citations
9

35 Citations

A synthetic small molecule for rapid induction of multiple pluripotency genes in mouse embryonic fibroblasts

A novel compound termed, δ is identified that could dramatically induce the endogenous expression of Oct-3/4 and Nanog and rapidly overcame the rate-limiting step of epithelial transition in cellular reprogramming by switching the complex transcriptional gene network.

A synthetic small molecule for targeted transcriptional activation of germ cell genes in a human somatic cell.

The remarkable ability of the SAHA-PIP K, which was developed as part of a SAHA–PIP library (A to F), to trigger targeted transcriptional activation of germ-cell-specific and PIWI-pathway genes in HDFs is demonstrated and a small molecule that has access to both the genetic and epigenetic environment is developed.

Identification of a small molecule that turns ON the pluripotency gene circuitry in human fibroblasts.

A targeting small molecule called SAHA-PIP comprising the histone deacetylase inhibitor SAHA and the sequence-specific DNA binding pyrrole-imidazole polyamides for modulating distinct gene networks is developed and identified.

Distinct DNA-based epigenetic switches trigger transcriptional activation of silent genes in human dermal fibroblasts

The remarkable ability of thirty-two different SAHA-PIPs to trigger the transcriptional activation of exclusive clusters of genes and noncoding RNAs is demonstrated for the first time.

Chemical Modification of a Synthetic Small Molecule Boosts Its Biological Efficacy against Pluripotency Genes in Mouse Fibroblasts

The biological activity was significantly improved against the core pluripotency genes after the incorporation of an isophthalic acid (IPA) at the C terminus and the resultant IPA conjugate dramatically induced Oct‐3/4 and demonstrated a new chemical strategy for developing PIP conjugates as next‐generation genetic switches.

Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature

There is a need to develop therapeutic strategies that effectively mimic the natural environment and include the ways to modulate the gene expression at both the genetic and epigenetic levels, and the development of tailor-made small molecules that could epigenetically alter DNA in a sequence-specific manner is a promising approach.

Synthesis and biological evaluation of a targeted DNA-binding transcriptional activator with HDAC8 inhibitory activity.

Chemical Control System of Epigenetics.

The chemical aspects of the natural epigenetic control system are summarized and the recent advances in the synthetic strategies to mimic the genetic and epigenetic Control system are detailed.

Clinical grade iPS cells: need for versatile small molecules and optimal cell sources.

Cellular reprogramming for pancreatic β-cell regeneration: clinical potential of small molecule control

A comprehensive overview of the available transcription factors, small molecules and reprogramming strategies available for pancreatic β-cell regeneration, this review compiles the current progress made towards the generation of clinically relevant insulin-producing β-cells.

References

SHOWING 1-10 OF 84 REFERENCES

Synthetic Small Molecules for Epigenetic Activation of Pluripotency Genes in Mouse Embryonic Fibroblasts

Ch Chromatin immunoprecipitation analysis suggested that SAHA–PIP‐mediated gene induction proceeds by histone H3 Lys9 and Lys14 acetylation and Lys4 trimethylation, which are epigenetic features associated with transcriptionally active chromatin.

Development of programmable small DNA-binding molecules with epigenetic activity for induction of core pluripotency genes.

Promotion of Reprogramming to Ground State Pluripotency by Signal Inhibition

It is reported that brain-derived neural stem (NS) cells acquire undifferentiated morphology rapidly and at high frequency after a single round of transduction with reprogramming factors.

Reprogramming of murine fibroblasts to induced pluripotent stem cells with chemical complementation of Klf4

A small-molecule screening platform applied to identify compounds that functionally replace the reprogramming factor Klf4 gave rise to iPS cells that are indistinguishable from murine embryonic stem cells, and can be used to screen large chemical libraries in search of novel compounds to replace theReprogramming factors that induce pluripotency.

Chromatin structure of pluripotent stem cells and induced pluripotent stem cells.

Recent studies that provide a genome-wide view of the chromatin structure signature in ES cells and iPS cells are discussed and that highlight the central role of histone modifiers and chromatin remodelers in pluripotency maintenance and induction are discussed.

A small-molecule inhibitor of tgf-Beta signaling replaces sox2 in reprogramming by inducing nanog.

Radical Acceleration of Nuclear Reprogramming by Chromatin Remodeling with the Transactivation Domain of MyoD

Radical acceleration of iPSC creation is demonstrated with a fusion gene between Oct4 and the powerful transactivation domain (TAD) of MyoD (M3O) and the approach of fusing TADs to unrelated transcription factors has far‐reaching implications as a powerful tool for transcriptional reprogramming beyond application to iPSCs.

Brief Report: Combined Chemical Treatment Enables Oct4‐Induced Reprogramming from Mouse Embryonic Fibroblasts

It has been established that exogenous expression of four transcription factors (Oct4, Klf4, Sox2, and c‐Myc) can reprogram mammalian somatic cells to pluripotent states. Further studies demonstrated…

piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells

It is shown that the individual PB insertions can be removed from established iPS cell lines, providing an invaluable tool for discovery, and the traceless removal of reprogramming factors joined with viral 2A sequences delivered by a single transposon from murine iPS lines is demonstrated.

Scanning the human genome with combinatorial transcription factor libraries

Large combinatorial libraries of artificial transcription factors comprising three or six zinc-finger domains are prepared, and selected transcription factor–DNA interactions able to upregulate several genes in human cells are selected.
...