Biophysical Society Thematic Meeting| Santa Cruz 2018

Genome Biophysics: Integrating Genomics and Biophysics to Understand Structural and Functional Aspects of Genomes

Tuesday Speaker Abstracts

Genomic Rearrangement Induced Gene Activation by Architectural Stripes Katerina Kraft 1,2 ; Andreas Magg 2 ; Verena Heinrich 2 ; Christina Riemenschneider 2 ; Robert Schoepflin 2 ; Stefan Mundlos 2 ; 1 Stanford, , Stanford, California, United States 2 MPIMG, , Berlin, Berlin, Germany Precise spatiotemporal gene expression is essential for normal organismal development and homeostasis and requires regulation at many levels. At one level, cis-regulatory elements, enhancers, drive the cell-type- and time-specific expression of developmental genes. These long- range enhancers confer their activity on genes via chromatin looping and this 3d chromatin structure constrains enhancer activity to the target genes. In recent years many architectural units have been defined based on hic, a number of which regulate enhancer-promoter communication. This includes architectural stripes, which were characterized in a recent in vitro study. Here we induce serial genomic invertions in vivo in embryonic limb buds, and observe the formation of tissue specific architectural stripes by capture hic. We find the enhancer at the inversion point is able to communicate aberrantly with several promoters inside an architectural stripe leading to congenital limb malformation. Deletion of the stripe anchor point results in stripe collapse, leading to significant expression changes and rescue of the skeletal phenotype. This study sheds light on the mechanism by which structural variations inducing architectural stripes control several important developmental genes within the stripe. Moreover, it suggests a general mechanism explaining connection between chromatin architecture and gene expression. This work opens up the discussion of enhancer-promoter specificity, a new uncharacterized field.

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