A Neat Tug to Move a Gene
Amanda Coutts, 15/11/11
The regulation of gene expression is a complex process and one that is incompletely understood. Precise control of gene expression is crucial for proper development and is required to keep us healthy.
Gene expression is regulated on a variety of levels by proteins such as transcription factors that can turn expression of a gene 'on' or 'off' and signalling pathways. Ultimately the cell must decipher all the signals and coordinate the various players to decide whether to turn gene expression on (activation) or off (repression).
To make a protein, cells first read our DNA code and transcribe it to make the corresponding RNA (referred to as messenger 'm' RNA). The mRNA is then translated to produce the corresponding protein(s) (Fig 1). Scientists have also more recently discovered that a large proportion of our RNA does not code for a protein and is referred to as noncoding (nc). The challenge is to understand what, if any, function can be ascribed to these ncRNAs and how they might influence gene expression.
Gene expression is regulated on a variety of levels by proteins such as transcription factors that can turn expression of a gene 'on' or 'off' and signalling pathways. Ultimately the cell must decipher all the signals and coordinate the various players to decide whether to turn gene expression on (activation) or off (repression).
To make a protein, cells first read our DNA code and transcribe it to make the corresponding RNA (referred to as messenger 'm' RNA). The mRNA is then translated to produce the corresponding protein(s) (Fig 1). Scientists have also more recently discovered that a large proportion of our RNA does not code for a protein and is referred to as noncoding (nc). The challenge is to understand what, if any, function can be ascribed to these ncRNAs and how they might influence gene expression.
A recent paper from Michael G Rosenfeld's group at the University of California, San Diego, published in the Nov. 11 issue of Cell (1) describes how two ncRNAs, NEAT2 and TUG1 play an important role in controlling gene expression.
This group found that a protein, Pc2, specifically associated with TUG1 under conditions of reduced cell growth, where it acted to repress transcription of genes involved in growth control. Under conditions of enhanced cell growth, Pc2 relocated within the nucleus where it was associated with a different ncRNA, NEAT2, to enhance transcription of growth control genes.
Moreover, the researchers also found that Pc2 was bound to TUG1 when it was methylated (a post-translational modification involving transfer of a methyl group to a specific lysine residue in Pc2 protein sequence) and bound to NEAT2 when it was demethylated.
Now here's the twist: Pc2 is controlling the same set of genes in the two different locations within the nucleus; one called PcG which is a 'repressive' environment and one called ICG which is an 'active' environment. It turns out that the methylation state of Pc2 and it's interaction with either TUG1 or NEAT2 results in the relocation of this group of genes from one nuclear compartment to another to influence their expression (Fig 2).
As recent evidence suggests that the majority of our genetic material is transcribed into ncRNA, most of which have an unknown function, this 'dark matter of our genome' will no doubt provide us with many more fascinating scientific discoveries.
(1) ncRNA- and Pc2 Methylation-Dependent Gene Relocation between Nuclear Structures Mediates Gene Activation Programs. L Yang et al., Cell 147, 773–788, November 11, 2011.
This group found that a protein, Pc2, specifically associated with TUG1 under conditions of reduced cell growth, where it acted to repress transcription of genes involved in growth control. Under conditions of enhanced cell growth, Pc2 relocated within the nucleus where it was associated with a different ncRNA, NEAT2, to enhance transcription of growth control genes.
Moreover, the researchers also found that Pc2 was bound to TUG1 when it was methylated (a post-translational modification involving transfer of a methyl group to a specific lysine residue in Pc2 protein sequence) and bound to NEAT2 when it was demethylated.
Now here's the twist: Pc2 is controlling the same set of genes in the two different locations within the nucleus; one called PcG which is a 'repressive' environment and one called ICG which is an 'active' environment. It turns out that the methylation state of Pc2 and it's interaction with either TUG1 or NEAT2 results in the relocation of this group of genes from one nuclear compartment to another to influence their expression (Fig 2).
As recent evidence suggests that the majority of our genetic material is transcribed into ncRNA, most of which have an unknown function, this 'dark matter of our genome' will no doubt provide us with many more fascinating scientific discoveries.
(1) ncRNA- and Pc2 Methylation-Dependent Gene Relocation between Nuclear Structures Mediates Gene Activation Programs. L Yang et al., Cell 147, 773–788, November 11, 2011.
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