Expanding the mesodermal transcriptional network by genome‐wide identification of Zinc finger homeodomain 1 (Zfh1) targets

Abstract

The Drosophila transcription factor (TF) Zfh1 has distinct roles compared to the cell lineage‐determining TFs in almost all mesoderm‐derived tissues. Here, we link Zfh1 to the well‐characterized mesodermal transcriptional network. We identify five enhancers integrating upstream regulatory inputs from mesodermal TFs and directing zfh1 expression in mesoderm. Most downstream Zfh1‐target genes are co‐bound by mesodermal TFs, suggesting that Zfh1 and mesodermal TFs act on the same sets of co‐regulated genes during the development of certain mesodermal tissues. Furthermore, we demonstrate that Zfh1 is critical for the expression of a hemocyte marker gene peroxidasin and helps restrict the activity of a hemocyte‐specific enhancer of serpent to hemocyte‐deriving head mesoderm, suggesting a potential role of Zfh1 in hemocyte development.

Two sequential gene expression programs bridged by cell division support long-distance collective cell migration

“…Using the available ChIP data relating to these four TFs (i.e. Zfh1, Bin, Mef2 and Doc2; Jakobsen et al, 2007 ; Zinzen et al, 2009 ; Junion et al, 2012 ; Wu et al, 2019 ), we scanned for their co-occupancy to DNA sequences flanking 16 genes that had previously been confirmed to be expressed in actively migrating CVM cells during stages 10-13 ( Bae et al, 2017 ). Enhancers regulating HLH54F and Doc2 had been identified previously ( Ismat et al, 2010 ; Kadam et al, 2012 ).…”

“…Predictions for CVM-specific enhancer elements were generated using 6-8 h ChIP-ChIP data for Zfh1 ( Wu et al, 2019 ), Bin ( Zinzen et al, 2009 ), Mef2 ( Zinzen et al, 2009 ) and Doc2 ( Junion et al, 2012 ). Priority was given to regions that showed occupancy by both Bin and Mef2 while excluding Twi ( Zinzen et al, 2009 ).…”

Interaction between Ras and Src clones causes interdependent tumor malignancy via Notch signaling in Drosophila

“…In mammals, ZEB1 represses transcription of epithelial determinants such as E-cadherin and Crumbs3 (Caramel et al, 2018). Similarly, in Drosophila, it has been shown by DamID-seq and ChIP-seq analyses that the E-cadherin gene shotgun (shg) is a direct target of Zfh1 (Albert et al, 2018;Wu et al, 2019). We found that expression of shg, which was detected by the shg-lacZ reporter (Genevet et al, 2009), was significantly downregulated by overexpression of Zfh1 (Figure 3M, compare with Figure 3L, quantified in Figure 3N).…”

“…Notably, Zfh1 blocks cell death of Src-activated cells by repressing hid. Zfh1 also prevents cell death by repressing rpr (Ohayon et al, 2009;Wu et al, 2019). Given that hid and rpr drive apoptosis of ''loser cells'' in cell competition (Nagata and Igaki, 2018), Zfh1 may also contribute to tumor progression via regulation of cell competition.…”

Drosophila, an Integrative Model to Study the Features of Muscle Stem Cells in Development and Regeneration

“…ZEB is well known for triggering epithelial-to-mesenchymal transitions (EMT) in both developing embryos and cancer cells [74][75][76]. Zfh1 is also known to regulate mesoderm patterning in the embryo and adult intestinal stem cells [77,78]. Zfh1 is expressed in all AMPs during embryonic/larval development (Figure 1) [67] and persists in the adult MuSCs, where it is required to prevent differentiation and maintain stemness (Figure 2A) [16,17].…”