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

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Computation to unravel how genes are regulated and shed light on how

cells become different

http://www.eurekalert.org/pub_releases/2008-04/esf-ctu041008.php

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 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.