Chromatin Plasticity Characterizes the Embryonic Stem Cell Nucleus

A recent paper presented new insights into the mechanisms that control chromatin plasticity in human embryonic stem cells and that allow these cells to differentiate in to many different types of tissue.

Investigators at the Hebrew University of Jerusalem (Israel) employed molecular, microscopic, and genomic approaches to compare the nature of chromatin (DNA, RNA, and protein) in embryonic stem cells (ESCs) to that found in mature, differentiated cells.

They reported in the June 19, 2012, issue of the journal Nature Communications that the use of epigenetic drugs and mutant ESCs lacking various chromatin proteins revealed that histone acetylation, G9a-mediated histone H3 lysine 9 (H3K9) methylation, and lamin A expression, all affected chromatin protein dynamics.

Histone acetylation controlled, almost exclusively, euchromatin protein dynamics. Euchromatin comprises the most active portion of the genome within the cell nucleus. It is a lightly packed form of chromatin that is rich in gene concentration, and is often under active transcription.

Lamin A expression regulates heterochromatin protein dynamics. Heterochromatin is tightly coiled chromosomal material that stains deeply during interphase and is believed to be genetically inactive. In differentiated cells, lamin A binds compacted domains of chromatin and anchors them to the cell’s nuclear envelope. Lamin A was not found in ESCs, which seems to generate a more dynamic chromatin state in the ESC nucleus.

G9a, the histone-lysine N-methyltransferase also known as H3 lysine-9 specific 3, regulates both euchromatin and heterochromatin protein dynamics.

In contrast, the investigators found that DNA methylation and nucleosome repeat length had little or no effect on chromatin-binding protein dynamics in ESCs. Altered chromatin dynamics associated with perturbed ESC differentiation.

“If we can apply this new understanding about the mechanisms that give embryonic stem cells their plasticity, then we can increase or decrease the dynamics of the proteins that bind DNA and thereby increase or decrease the cells’ differentiation potential,” said senior author Dr. Eran Meshorer, professor of genetics at the Hebrew University of Jerusalem. “This could expedite the use of embryonic stem cells in cell therapy and regenerative medicine, by enabling the creation of cells in the laboratory which could be implanted in humans to cure diseases characterized by cell death, such as Alzheimer's, Parkinson's, diabetes, and other degenerative diseases.”

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