Epigenetics and chromatin

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Most people are aware that DNA encodes the information that controls the development and function of all living organisms. This information is organised into regions called genes and the complement of DNA information that exists in any organism is known as its genome.

In complex multicellular organisms such as humans, the genome is a database of master plans for the entire body. But more than a decade since the human genome was decoded, several fundamental questions regarding genome regulation remain largely unanswered.

What controls the development of more than 200 distinct cell types from a common source of genetic information? How are genes that serve special roles in the pancreas or brain prevented from being ‘switched on’ in other organs? And why does the activity of some important genes change in diseases such as cancer and diabetes?

We now know that these questions cannot be answered solely by understanding the DNA code. The exciting field of epigenetics is at the frontier of research into the essential processes that control genes and how these differ between cell types under normal and disease conditions.

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Chromatin conformation and DNA accessibility are central to gene expression

Found on http://fortyfourandtwo.blogspot.nl/2014/07/context-and-architecture-complexities.html


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The chromatin polymer is a dynamic assembly of DNA and various nuclear proteins that spatially regulates eukaryotic gene transcription by structural adaptation and genome compartmentalisation.

Gene expression is primarily regulated by chromatin accessibility. A relaxed chromatin structure where DNA is loosely associated with nucleosomes (euchromatin) is permissive to the transcriptional machinery, allowing the synthesis of RNA. By contrast, genes are silenced when DNA is tightly wrapped around histones and buried within the chromatin (heterochromatin).

It is by selective activation and silencing of different genes that more than 200 distinct cell types of the human body are derived from a single source of genetic information. Furthermore, chromatin dynamics provides the adaptive agency for cells to manage environmental variations with rapid changes in gene expression.

Small chemical modifications that decorate the chromatin landscape distinguish active and silent genomic regions. Modifications frequently occur at specific amino acid residues on histones as well as the DNA itself to collectively comprise the epigenome. By several distinct mechanisms, the chemical signatures of chromatin architectures are fundamental to gene expression. Individual modifications can recruit functional complexes responsible for the structural reorganisation of chromatin. Other modifications directly affect the stability of the histone-DNA complex to promote an open conformation. These gene-regulatory effects in combination with substantial functional interplay between histone modifications has lead to the proposition of a chromatin code that greatly extends the information potential of the genetic code by shaping transcriptional competency.

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Epigenetic changes can regulate transitions between active and inactive states of gene expression

Found on http://fortyfourandtwo.blogspot.nl/2014/07/context-and-architecture-complexities.html

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Technology has undoubtedly transformed the way we interact with the world.

The ability to digitally organise, filter, and efficiently use the immense data we generate affects many aspects of our lives from marketing to social policy. Similarly, the realm of biological research has been revolutionised by technological innovations of the digital age.

Major advances in DNA sequencing technologies, such as greater speed and affordability, have ensured that whole or partial genome analysis has become a common feature of many biological studies. Combined with improved methods for measuring other important components of cell function in large volumes, never before have scientists had access to so much biological information.

With the ability to gather such unprecedented amounts of data, the re-focusing of researchers to systems-level investigations promises a remarkable increase in our capacity for biological discovery. While this is new territory for most biologists, the use of computational methods, tools, databases, and online resources is helping to translate this plethora of information to real scientific knowledge.

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Mapping cell-specific chromatin changes

Found on http://fortyfourandtwo.blogspot.nl/2015/02/mapping-cell-specific-histone.html

Genome-wide distribution of histone methylation

Found on http://circres.ahajournals.org/content/116/4/715.full?sid=747b2a6d-88cf-47cf-9b9a-633b98ed2d4a

Epigenetics in human health and disease

Found on http://fortyfourandtwo.blogspot.nl/2014/07/context-and-architecture-complexities.html


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Some experiences are harder to forget than others.
The genome's ability to adapt to environmental changes also has a dark side. Emerging research is beginning to unravel an extraordinary phenomenon of cellular memory centred on the field of chromatin biology. One where periods of challenging metabolic conditions can initiate programs of gene expression that dramatically increase the risk for disease later in life.

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