Computation to unravel how genes are regulated and shed light on how cells become different

A closer alliance between computational and experimental researchers is needed to make progress towards one of biology’s most challenging goals, understanding how epigenetic marks contribute to regulation of gene expression. This emerged from a recent workshop organised by the European Science Foundation (ESF), “Computational Approaches to the Role of Epigenetic Marks in Transcription Regulation”.

Epigenetics studies features of the DNA and chromatin that are stably inherited through cell division but that are beyond the DNA sequence itself. It has been well established that epigenetic features influence the transcription process whereby the DNA sequences of genes are translated into the RNA and protein products that determine structure and function. Just as crucially, it is believed that epigenetics also allows changes to these gene expression patterns to be remembered, so that different organs and tissues can emerge during embryonic development, and retain their identity and function for the rest of the organism’s lifetime.

Changes in gene expression can result from modifying chromatin, which is the structure comprising proteins and DNA that is the repository for genetic information. Marks are imposed that serve as templates for modification of the chromatin, altering the ability of genes to be accessed by the DNA transcription machinery. The result is that some genes are suppressed and others are silenced altogether. One of the key questions discussed at the ESF workshop concerned how these changes are “remembered” during cell division through replication of the epigenetic marks, and yet how in some cases these can be reversed, allowing a cell to be reprogrammed so that it can take on a different role or function.

The ability of cells to be reprogrammed by having epigenetic marks removed is of great interest and importance in stem cell research, said Erik van Nimwegen from University of Basel in Switzerland, convenor of the ESF workshop. In some cases cells can be “de-differentiated” in this way, losing their normal function and becoming stem cells again, capable of subsequently dividing into different cell types by acquiring once again appropriate controls over expression of their genes.

The ability to lose as well as gain epigenetic marks that constrain the expression of certain genes is also important in early embryonic development, when rapid changes in structure and function are occurring. One presentation at the workshop by Dirk Schübeler of the Friedrich Miescher Institute in Basel described how whole sets of genes can have their expression modified just temporarily through the process of DNA methylation, one of the main mechanisms for blocking access to the underlying DNA of a gene.

But with so much still to be discovered about the complex and subtle nature of gene regulation through epigenetic modification, the greatest triumph of the ESF workshop lay not so much in the individual presentations, but the collective decisions over future research priorities, and the relationships established between computational and experimental biologists.

“We think that the discussions among experimentalists and theorists regarding interesting outstanding questions has shaped the planning for future research of all participants,” said van Nimwegen. “Several participants felt the workshop was rather unique in that it brought together a wide variety of researchers working in a field that is rather new.”

Experiments and observation provide the data about gene expression patterns, while computational methods analyse the changes over time and help identify sequences that have been in effect memorised, and others that have been “forgotten”. This phenomenon whereby cells in effect remember what has happened to them and respond through changes in their expression is fundamental to development of organisms, along with their structure and function during their lifetime, as well as inheritance of adaptations to environmental factors.

Source: European Science Foundation

Related stories:

Study identifies changes to DNA in major depression and suicide
Autopsies usually point to a cause of death but now a study of brain tissue collected during these procedures, may explain an underlying cause of major depression and suicide. The international research group, led by Dr. Michael O. Poulter of Robarts Research Institute at The University of Western Ontario and Dr. Hymie Anisman of the Neuroscience Research Institute at Carleton University, is the first to show that proteins that modify DNA directly are more highly expressed in the brains of people who commit suicide.
'Addicted' cells provide early cancer diagnosis
Scientists at the Institute of Food Research have detected subtle changes that may make the bowel more vulnerable to the development of tumours.
MicroRNA controls expression of oncogenes
A new study demonstrates that microRNAs can modulate the expression of well known tumor-specific oncogenic translocation proteins and may play a significant role in some human cancers. The research, published by Cell Press in the June issue of the journal Cancer Cell, is likely to lead to new strategies for treating some specific lymphomas and leukemias.
Scientists trace causal link between a tumor suppressor gene and liver cancer
Scientists at Cold Spring Harbor Laboratory (CSHL) have taken the search for cancer-causing genes an important step forward. In a newly published paper, they confirm that a gene called DLC1 is a tumor suppressor. They have demonstrated in living mice that its deletion, inactivation or loss precipitates events culminating in an aggressive type of liver cancer closely related to common human epithelial cancers of the liver (also known as hepatocellular carcinoma, or HCC).
New insights into cellular reprogramming revealed by genomic analysis
The ability to drive somatic, or fully differentiated, human cells back to a pluripotent or “stem cell” state would overcome many of the significant scientific and social challenges to the use of embryo-derived stem cells and help realize the promise of regenerative medicine.
Traditional herbal medicine kills pancreatic cancer cells, researchers report
An herb used in traditional medicine by many Middle Eastern countries may help in the fight against pancreatic cancer, one of the most difficult cancers to treat. Researchers at the Kimmel Cancer at Jefferson in Philadelphia have found that thymoquinone, an extract of nigella sativa seed oil, blocked pancreatic cancer cell growth and killed the cells by enhancing the process of programmed cell death.
'Destruct' triggers may be jammed in tumor cells, UF geneticists say
Tumor cells living in the cross hairs of radiation or chemotherapy may be able to escape death because their self-destruct mechanisms are jammed, say University of Florida scientists writing in a recent issue of Developmental Cell.
Epigenetic research uncovers new targets for modification enzymes
Enzymes regulating genetic expression can be just as important as the genome itself, increasing evidence shows. The expanding field of epigenetics focuses on the multiple influences on DNA and surrounding molecules that determine whether genes are turned on or off during development and disease processes.

News discussion:

General Science news