13 May 2019

How does the same DNA sequence generate hundreds of cell types with diverse morphologies and functions? Transcriptional enhancers are thought to provide part of the answer to this central question in biology. These regulatory elements interact with promoters and other enhancers to generate a complex and cell-specific network of chromatin interactions.

This interaction network is crucial for proper regulation of gene expression and 3D genome organization. How enhancers are regulated during early embryonic development, however, is not well understood. This is particularly hindered by the difficulty in performing genome wide studies in the early embryo. In this regard, embryonic stem cells (ESCs) derived from early developmental stages provide a great model for understanding early embryonic development and the basic mechanisms of gene regulation.

In Nature Cell Biology, Yaser Atlasi, Wout Megchelenbrink and colleagues from the group of Henk Stunnenberg, theme Cancer development and immune defense, plublished a combination of experimental and bioinformatic approaches to study enhancer regulation in different states of embryonic stem cells. Using state-of-the-art genome wide technologies, the team described the chromatin interaction network in two distinct states of ESCs. Unexpectedly, the team found that the enhancer-promoter interactions are largely preserved between the two states, notwithstanding the extensive epigenetic changes that culminate in distinct transcriptional programs. Further, the transcription factor estrogen receptor related beta (ESRRB) was shown to play a key role in enhancer activation.
 
This detailed and comprehensive picture of the enhancer landscape provides a deeper understanding of gene regulation during early development and may shed light on how mutations within enhancers contribute to developmental defects.

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