ETS transcription factors regulate precise matrix metalloproteinase expression and follicle rupture in Drosophila.

Drosophila matrix metalloproteinase 2 (MMP2) is specifically expressed in posterior follicle cells of stage-14 egg chambers (mature follicles) and is crucial for the breakdown of the follicular wall during ovulation, a process highly conserved from flies to mammals. It remains unknown what factors regulate spatiotemporal expression of MMP2 in follicle cells. Here, we demonstrated critical roles for the ETS-family transcriptional activator Pointed (Pnt) and its endogenous repressor Yan in regulating MMP2 expression. Pnt is expressed in posterior follicle cells and overlaps with MMP2 expression in mature follicles. Genetic analysis demonstrated that pnt is both required and sufficient for MMP2 expression in follicle cells. In addition, Yan is temporally upregulated in stage-13 follicle cells to fine-tune Pnt activity and MMP2 expression. Furthermore, we identified a 1.1 kb core enhancer that is responsible for the spatiotemporal expression of MMP2 and contains multiple pnt/yan binding motifs. Mutation of pnt/yan binding sites significantly impaired the mmp2 enhancer activity. Our data reveal a novel transcriptional regulation of mmp2 expression in Drosophila ovulation, which could be conserved in other biological systems.