BioEssays 6∕2013

Changing the landscape may lead to disease . On pages 533–543 of this issue, Malte Spielmann and Stefan Mundlos discuss how structural variations in regulatory parts of the genome can interfere with normal gene regulation and – by doing so – cause disease. The upper part of the cover shows a wild type situation in which a chromosomal looping mechanism involving the binding of transcription factors (TF) brings the enhancer (red) close to the promoter of its target gene leading to tissue‐specifi c expression. In the lower part, the enhancer is duplicated, resulting in disturbed gene expression. Other structural variations that can change the regulatory landscape include the deletion∕mutation of enhancer elements or their inversion, and the deletion of insulators (green bar in the cover image). Cover by Malte Spielmann and Stefan Mundlos.