October 04, 2007

Human embryonic stem cells remain embryonic because of epigenetic factors

A human embryonic stem cell is reined in – prevented from giving up its unique characteristics of self-renewal and pluripotency – by the presence of a protein modification that stifles any genes that would prematurely instruct the cell to develop into heart or other specialized tissue.
Thanks to the simultaneous presence of different protein modifications, stem cells are primed and poised, ready to develop into specialized body tissue, Singapore scientists reported in last month’s issue of the journal Cell Stem Cell.

The molecules central to this balancing act, H3K4me3 and H3K27me3, are among the so-called epigenetic modifications that influence the activity patterns of genes in both human embryonic stem (ES) cells and mature human adult cells.

His GIS colleague, Wei Chia-Lin, Ph.D., who headed the Singapore research team, said, “This study demonstrates the power of a whole genome and robust sequencing technology, when applied in the epigenetic analysis of ES cells, can reveal features of the genomes that were not previously appreciated. The new knowledge and target candidate genes resulted from such unbiased study are ultimately important for researchers to understand the fundamental nature of stem cell proliferation and differentiation.”

Drs. Wei and Ng and the other researchers used cutting-edge technologies developed at GIS, to sequence, or decipher, the DNA of human ES cells. With the sequence data in hand, the scientists were able to categorize the genes into three groups, each modified by different combinations of the two epigenetic markers.

The researchers discovered that the majority of the regions in the genome harbor active histone marks that act as sign posts and allow cells to quickly find genes “to turn on” or activate them.

Identifying the locations of these genomic signposts will also be crucial for discovering human genes that are important for different functions in ES cells.

Of the two epigenetic markers, H3K4me3 was found to be the most prevalent – the scientists reported and noted that it occurs near the DNA areas that are promoters of two-thirds of human genes. Of the 17,469 nonredundant unique human genes that the scientists sequenced, 68% contained H3K4me3, and only 10% contained overlapping H3K27me3.

More information about epigenetic modifications:

In living cells, DNA is packaged along with histone proteins, which are chief protein components that act as spools around which DNA winds. The histone proteins are decorated with different marks, which can affect the various activities of the modified DNA such as transcription, gene silencing, imprinting and replication. Such marks key roles in the process of cellular differentiation, allowing cells to maintain different characteristics despite containing the same genomic material. While different cells can have identical genetic DNA sequences, their characteristics and differentiation patterns are influenced by the different marks on the histone proteins. Therefore, histone marks represent an epigenetic marker or code that can be used by the cells to expand their plasticity and complexity.