Stable binding of the conserved transcription factor grainy head to its target genes throughout Drosophila melanogaster development

Markus Nevil, Eliana R. Bondra, Katharine N. Schulz, Tommy Kaplan, Melissa M. Harrison*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

It has been suggested that transcription factor binding is temporally dynamic, and that changes in binding determine transcriptional output. Nonetheless, this model is based on relatively few examples in which transcription factor binding has been assayed at multiple developmental stages. The essential transcription factor Grainy head (Grh) is conserved from fungi to humans, and controls epithelial development and barrier formation in numerous tissues. Drosophila melanogaster, which possess a single grainy head (grh) gene, provide an excellent system to study this conserved factor. To determine whether temporally distinct binding events allow Grh to control cell fate specification in different tissue types, we used a combination of ChIP-seq and RNA-seq to elucidate the gene regulatory network controlled by Grh during four stages of embryonic development (spanning stages 5–17) and in larval tissue. Contrary to expectations, we discovered that Grh remains bound to at least 1146 genomic loci over days of development. In contrast to this stable DNA occupancy, the subset of genes whose expression is regulated by Grh varies. Grh transitions from functioning primarily as a transcriptional repressor early in development to functioning predominantly as an activator later. Our data reveal that Grh binds to target genes well before the Grh-dependent transcriptional program commences, suggesting it sets the stage for subsequent recruitment of additional factors that execute stage-specific Grh functions.

Original languageAmerican English
Pages (from-to)605-620
Number of pages16
JournalGenetics
Volume205
Issue number2
DOIs
StatePublished - Feb 2017

Bibliographical note

Publisher Copyright:
© 2017 by the Genetics Society of America.

Keywords

  • Drosophila
  • Epithelial cell fate
  • Pioneer factor
  • Transcription

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