Distinct in vivo requirements for establishment versus maintenance of transcriptional repression

Abstract

Low-level ectopic expression of the Runt transcription factor blocks activation of the Drosophila melanogaster segmentation gene engrailed (en) in odd-numbered parasegments and is associated with a lethal phenotype. Here we show, by using a genetic screen for maternal factors that contribute in a dose-dependent fashion to Runt-mediated repression, that there are two distinct steps in the repression of en by Runt. The initial establishment of repression is sensitive to the dosage of the zinc-finger transcription factor Tramtrack. By contrast, the co-repressor proteins Groucho and dCtBP, and the histone deacetylase Rpd3, do not affect establishment but instead maintain repression after the blastoderm stage. The distinction between establishment and maintenance is confirmed by experiments with Runt derivatives that are impaired specifically for either co-repressor interaction or DNA binding. Other transcription factors can also establish repression in Rpd3-deficient embryos, which indicates that the distinction between establishment and maintenance may be a general feature of eukaryotic transcriptional repression.

Transcription ofDrosophilaTroponin I Gene Is Regulated by Two Conserved, Functionally Identical, Synergistic Elements

“…Maintenance, however, does not seem to rely exclusively on this transcription factor. The difference between these two types of transcription has been recently documented (Wheeler et al, 2002), and the present case may indicate that it is a general phenomenon. Because the analyzed regions contain canonical binding sites for TINMAN and BINIOU, it seems puzzling why these factors are not able to drive gene expression in a mef2 null background.…”

RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription

“…Runt either activates or represses transcription in a promoteror enhancer-specific context and cell type-specific manner, but more frequently it is required for repressing transcription (Wheeler et al, 2002;Swantek and Gergen, 2004). For instance, during embryogenesis the establishment of Runt-mediated repression of engrailed is dependent on the dosage of the zinc-fingercontaining transcription factor Tramtrack.…”

“…For instance, during embryogenesis the establishment of Runt-mediated repression of engrailed is dependent on the dosage of the zinc-fingercontaining transcription factor Tramtrack. However, the maintenance of repression of engrailed is dependent on the presence of the Groucho and dCtBP co-repressors and the Rpd3 histone deacetylase (Wheeler et al, 2002). Thus, Runt acts in a context-dependent manner, activating or repressing gene expression depending on the constitution of a particular promoter/enhancer or the availability of a given co-factor in a specific cell type.…”

Role of RUNX family members in transcriptional repression and gene silencing

“…These included Tramtrack (Ttk), a DNA-binding transcriptional repressor, the transcriptional corepressors dCtBP and Groucho, and the histone deacetylase Rpd3 (Wheeler et al, 2002). Embryos that were derived from females heterozygous for tramtrack restored engrailed expression in the gastrula stage in the presence of ectopic Runt.…”

“…engrailed is a segment polarity gene that is potently repressed by Runt in the gastrula and germband extension stages of embryogenesis. Using an inducible runt, even moderate levels of Runt led to constitutive repression of engrailed and embryonic lethality (Wheeler et al, 2002). Taking advantage of these phenotypes, a genetic screen was performed for factors that are required for repression by Runt.…”