The Histone Methyltransferases EHMT1 and EHMT2 Repress the Expression of Genes Related to Excitability and Cell Death in Oligodendrocyte Progenitors
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Histone mark H3K9me2 increases in oligodendrocyte progenitor cells (OPCs) after neuronal stimulation. This epigenetic modification, regulated by EHMT1/2 enzymes, impacts OPC cell death and electrical properties, influencing myelin basic protein (MBP) levels.
Area Of Science
- Neuroscience
- Epigenetics
- Cell Biology
Background
- Oligodendrocyte progenitor cells (OPCs) are electrically active and divide, responding to neuronal activity.
- Histone modifications play a crucial role in regulating gene expression during OPC development and response to stimuli.
Purpose Of The Study
- To investigate the role of the H3K9me2 histone mark and its associated enzymes (EHMT1/2) in proliferating OPCs.
- To determine how neuronal activity influences H3K9me2 levels in OPCs.
- To elucidate the impact of EHMT1/2-mediated H3K9me2 deposition on OPC gene expression, cell death, and electrical properties.
Main Methods
- Utilized optogenetic stimulation to activate neuronal activity in mice.
- Employed primary cultured OPCs with genetic deletion of Ehmt1 and Ehmt2.
- Applied pharmacological inhibition of EHMT enzymatic activity.
- Analyzed gene expression, cell death markers, receptor levels, cell counts, and myelin basic protein (MBP) levels.
Main Results
- H3K9me2 histone mark levels increased in proliferating OPCs following optogenetic stimulation of neuronal activity.
- EHMT1 and EHMT2 enzymes are critical for repressing genes involved in cell death and electrical properties in proliferating OPCs.
- Lineage-specific ablation of Ehmt1 and Ehmt2 resulted in increased cholinergic muscarinic receptors, decreased oligodendrocyte lineage cells, and reduced MBP levels.
Conclusions
- The repressive H3K9me2 histone mark is upregulated in proliferating OPCs in response to neuronal stimulation.
- EHMT1/2-mediated H3K9me2 is a key regulator of cell death pathways and proteins governing OPC electrical properties.
- These findings highlight an epigenetic mechanism linking neuronal activity to OPC function and myelination.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
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...
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...
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.