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Issue 121 Autumn 2016

Endocrinologist > Autumn 2016 > Hot topics

Controlling the stress response: a new hypothesis

| Hot topics

The glucocorticoid receptor (GR) binds to over 10,000 sites in the human genome, but is only known to regulate the expression of hundreds of genes. In this paper, Vockley et al. set out to discover the reason behind this discrepancy. To determine this, they measured the glucocorticoid (GC) responsive activity of nearly all GR binding sites (GBSs) captured using chromatin immunoprecipitation.

They found that only 13% of the sites assayed exhibited GC-induced activity. However, the 87% of sites that showed no GC-induced activity seemed to predominantly have epigenetic features of steady-state enhancers and were clustered around direct GBSs.

The authors hypothesise that their data support a model in which these clusters reflect interactions between direct and tethered GBSs over tens of kilobases. These interactions may synergistically modulate the activity of direct GBSs, and could therefore play a major role in driving gene activation in response to GCs and lead to a wider variety of stress responses that was previously thought.

Read the full article in Cell 2016 doi:10.1016/j.cell.2016.07.049

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