@article{ee3a57e369d74dcdb0f2a446ae7da9ea,
title = "GLI transcriptional repression regulates tissue-specific enhancer activity in response to hedgehog signaling",
abstract = "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 GLI binding 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 transcriptional activity in the mouse limb bud. They also retain H3K27ac enrichment in limb buds devoid of GLI activator and repressor, indicating that their activity is primarily regulated by GLI repression. Furthermore, 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 genes by altering the acetylation status at enhancers.",
author = "Lex, {Rachel K.} and Zhicheng Ji and Falkenstein, {Kristin N.} and Weiqiang Zhou and Henry, {Joanna L.} and Hongkai Ji and Vokes, {Steven A.}",
note = "Funding Information: We thank Blerta Xhemalce, Samantha Brugmann, Kevin Peterson and Janani Ramachandran for comments on the manuscript. We thank Drs. Ken Zaret, Maki Iwafuchi-Doi, Jongwhan Kim and Cathy Rhee for advice on performing ATAC-seq, Andy McMahon for providing the Gli3Flag mice and Jessica Podnar from the Genomic Sequencing and Analysis Facility at the University of Texas at Austin for technical advice. The Texas Advanced Computing Center (TACC) at The University of Texas at Austin provided computational resources. This work was supported by NIH R01HD073151 (to SAV and HJ), The St. Baldrick{\textquoteright}s Foundation (to SAV) and F31DE027597 (to RKL). Funding Information: We thank Blerta Xhemalce, Samantha Brugmann, Kevin Peterson and Janani Ramachandran for comments on the manuscript. We thank Drs. Ken Zaret, Maki Iwafuchi-Doi, Jongwhan Kim and Cathy Rhee for advice on performing ATAC-seq, Andy McMahon for providing the Gli3Flag mice and Jessica Podnar from the Genomic Sequencing and Analysis Facility at the University of Texas at Austin for technical advice. The Texas Advanced Computing Center (TACC) at The University of Texas at Austin provided computational resources. This work was supported by NIH R01HD073151 (to SAV and HJ), The St. Baldrick?s Foundation (to SAV) and F31DE027597 (to RKL). Eunice Kennedy Shriver National Institute of Child Health and Human Development. R01HD073151. Hongkai Ji Steven A Vokes. National Institute of Dental and Craniofacial Research. F31DE027597. Rachel K Lex. St. Baldrick?s Foundation. Steven A Vokes. National Institutes of Health. R01HG009518. Hongkai Ji. Publisher Copyright: {\textcopyright} Lex et al.",
year = "2020",
month = jan,
doi = "10.7554/eLife.50670",
language = "English (US)",
volume = "9",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}