Related Experiment Video
Updated: Apr 8, 2026
12:13
Zinc-finger Nuclease Enhanced Gene Targeting in Human Embryonic Stem Cells
Published on: August 23, 2014
11.3K
RING1B O-GlcNAcylation regulates gene targeting of polycomb repressive complex 1 in human embryonic stem cells.
Julien Jean Pierre Maury1, Chadi A El Farran2, Daniel Ng3
1Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668 Singapore; Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, 117575 Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, #08-01 Proteos, 138673 Singapore.
Stem Cell Research
|June 24, 2015
Summary
O-linked-N-acetylglucosamine (O-GlcNAc) modifies RING1B, an epigenetic regulator crucial for human embryonic stem cell (hESC) pluripotency and differentiation. Decreased O-GlcNAc on RING1B during differentiation may promote neuron development.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Post-Translational Modifications
Background:
- O-linked-N-acetylglucosamine (O-GlcNAc) is a dynamic post-translational modification regulating numerous cellular processes.
- O-GlcNAc's role in human embryonic stem cell (hESC) differentiation is emerging, but specific regulatory proteins remain unidentified.
Purpose of the Study:
- To identify O-GlcNAc-modified proteins involved in hESC regulation.
- To investigate the function of O-GlcNAc modification on RING1B during hESC differentiation.
Main Methods:
- Identification of O-GlcNAc proteins in hESCs.
- Site-directed mutagenesis to map O-GlcNAc sites on RING1B.
- Chromatin immunoprecipitation sequencing (ChIP-seq) to analyze RING1B binding.
- Analysis of O-GlcNAc levels during differentiation.
Main Results:
- hnRNP K, HP1γ, and RING1B were identified as O-GlcNAc-modified proteins in hESCs.
- Specific residues T(250)/S(251) and S(278) on RING1B are O-GlcNAcylated, with T(250)/S(251) O-GlcNAcylation decreasing during differentiation.
- O-GlcNAc modification influences RING1B-DNA binding, with distinct genomic enrichment patterns observed for modified versus unmodified RING1B near cell cycle and neuronal genes.
Conclusions:
- O-GlcNAc dynamically regulates RING1B, a key component of the Polycomb Repressive Complex 1 (PRC1).
- The decrease in RING1B O-GlcNAcylation during hESC differentiation may facilitate PRC1's target switching, promoting neuronal differentiation.
- O-GlcNAc modification of RING1B represents a novel regulatory mechanism contributing to hESC pluripotency maintenance and differentiation pathways.
Related Concept Videos
01:32Chromatin Modification in iPS Cells
2.3K
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...
2.3K
02:33Combinatorial Gene Control
10.0K
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.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
10.0K
01:29Somatic to iPS Cell Reprogramming
2.9K
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...
2.9K
01:14Maintenance of the ES Cell State
2.8K
The cells of the blastocyst inner cell mass only remain pluripotent for a short time. This state of pluripotency and self-renewal can be maintained in embryonic stem (ES) cell culture by adding specific chemicals or growth factors to ensure the cells can continue dividing and later differentiate into different cell types. In some cases, the cells are grown on a feeder layer of differentiated cells, which provides the growth factors and extracellular matrix components necessary for stem cell...
2.8K
01:37Epigenetic Regulation
4.2K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
4.2K
01:24Methods of Nuclear Reprogramming
2.3K
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...
2.3K