Researchers from University of Texas at Dallas collaborated with researchers from the Salk Institute for Biological Studies and other institutes for the first comprehensive analysis of epigenetic changes that play a critical role in human development.
Researchers from the University of Texas at Dallas and other renowned institutes like the Institute for Cancer Research, the University of California, the University of Wisconsin, and the Salk Institute for Biological Studies contributed to a multi-institutional group of scientists that have discovered the factors and epigenetic markers that contribute to the transformation and specialization of embryonic stem cells in human development. It was long believed that epigenetics (genes and factors influencing the expression of genes) play a remarkable role in the human development and evolution, but the exact biochemical mechanism was not known.
The professor and director of Salk’s Plant Molecular and Cellular Biology Laboratory and co- lead author of the research Joseph R. Ecker commented:
“Our findings help us to understand processes that occur during early human development and the differentiation of a stem cell into specialized cells, which ultimately form tissues in the body,”
Ecker is also holder of the Salk International Council Chair in Genetics. The results of this groundbreaking research were published on May 9th, in the renowned medical journal Cell.
The Essentials of the Research:
Renowned researchers like Pradipta Ray Ashwinikumar Kulkarni, Wen-Yu Chung, Zhenyu Xuan, and Michael Q. Zhang from the University of Texas at Dallas and other institutes established that proteins control and modulate gene expression of the DNA with the help of regulatory genes in response to environmental cues. Research suggests that epigenetic markers like DNA methylation and chromatin modifications maintain this process.
An epigenome that constitutes a wide variety of Epigenetic modifications controls cellular switching of genes with the help of biochemical processes without changing the DNA sequences. The researchers from the above-mentioned renowned institutes collectively worked at studying the physiological and biochemical states of different cells before specialization occurs. The researchers started with the most widely studied stem cell line, the H1 human embryonic stem cell, and studied the cell at various stages of development and specialization.
They observed that:
– Most regulatory genes have varying levels of C and G combinations for activation of DNA
– Methylation valleys or DMV are special regions or stretches of DNA that contains largest number of regulatory genes.
– DMV are usually devoid of methylation epigenetic modifications and are generally rich in CG sequences.
– Mature cells that have already been specialized into a certain type of cells tend to have lower CG levels and low DNA methylation activities suggesting that regulation of early and late embryonic stem cell differentiation is done by epigenetic mechanisms.
– The scientists concluded that chromatin modifications is the other epigenetic mechanism that control the expression of regulatory genes.
Ecker suggested that:
“If we understand how these cells’ lineages originate, we can understand if something goes right or wrong during differentiation. It’s a very basic study, but there are implications for being able to produce good quality cell types for various therapies.”
The results of this study are expected to help in understanding carcinogenesis in much detail as DMVs are normally unmethylated and thus inactive in most normal cells; however, a cell that has undergone malignant transformation express hypermethylated DMVs. Researchers suggest that understanding the metabolic and biochemical machinery of DNA methylation can help in understanding tumor development and enable scientists to devise functional and workable anti- tumor treatment plans.