PT  - JOURNAL ARTICLE
AU  - Rachel K. Lex
AU  - Zhicheng Ji
AU  - Kristin N. Falkenstein
AU  - Weiqiang Zhou
AU  - Joanna L. Henry
AU  - Hongkai Ji
AU  - Steven A. Vokes
TI  - GLI transcriptional repression regulates tissue-specific enhancer activity in response to Hedgehog signaling
AID  - 10.1101/732024
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 732024
4099  - http://biorxiv.org/content/early/2019/08/11/732024.short
4100  - http://biorxiv.org/content/early/2019/08/11/732024.full
AB  - Transcriptional repression needs to be rapidly reversible during embryonic development. This extends to the Hedgehog pathway, which primarily serves to counter GLI repression by processing GLI proteins into transcriptional activators. In investigating the mechanisms underlying GLI repression, we find that a subset of these regions, termed HH-responsive enhancers, specifically loses acetylation in the absence of HH signaling. These regions are highly enriched around HH target genes and primarily drive HH-specific limb activity. They also retain H3K27ac enrichment in limb buds devoid of GLI activator and repressor, indicating that their activity is primarily regulated by GLI repression. The Polycomb repression complex is not active at most of these regions, suggesting it is not a major mechanism of GLI repression. We propose a model for tissue-specific enhancer activity in which an HDAC-associated GLI repression complex regulates target gene expression by altering the acetylation status at enhancers.