Three distinct mechanisms, Notch instructive, permissive, and independent, regulate the expression of two different pericardial genes to specify cardiac cell subtypes.

Autor: Panta M; Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.; The Center for Genomic Advocacy, Indiana State University, Terre Haute, Indiana, United States of America., Kump AJ; Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.; The Center for Genomic Advocacy, Indiana State University, Terre Haute, Indiana, United States of America., Dalloul JM; The Center for Genomic Advocacy, Indiana State University, Terre Haute, Indiana, United States of America.; Terre Haute South Vigo High School, Terre Haute, Indiana, United States of America.; Stanford University, Stanford, California, United States of America., Schwab KR; Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.; The Center for Genomic Advocacy, Indiana State University, Terre Haute, Indiana, United States of America., Ahmad SM; Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.; The Center for Genomic Advocacy, Indiana State University, Terre Haute, Indiana, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Oct 27; Vol. 15 (10), pp. e0241191. Date of Electronic Publication: 2020 Oct 27 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0241191
Abstrakt: The development of a complex organ involves the specification and differentiation of diverse cell types constituting that organ. Two major cell subtypes, contractile cardial cells (CCs) and nephrocytic pericardial cells (PCs), comprise the Drosophila heart. Binding sites for Suppressor of Hairless [Su(H)], an integral transcription factor in the Notch signaling pathway, are enriched in the enhancers of PC-specific genes. Here we show three distinct mechanisms regulating the expression of two different PC-specific genes, Holes in muscle (Him), and Zn finger homeodomain 1 (zfh1). Him transcription is activated in PCs in a permissive manner by Notch signaling: in the absence of Notch signaling, Su(H) forms a repressor complex with co-repressors and binds to the Him enhancer, repressing its transcription; upon alleviation of this repression by Notch signaling, Him transcription is activated. In contrast, zfh1 is transcribed by a Notch-instructive mechanism in most PCs, where mere alleviation of repression by preventing the binding of Su(H)-co-repressor complex is not sufficient to activate transcription. Our results suggest that upon activation of Notch signaling, the Notch intracellular domain associates with Su(H) to form an activator complex that binds to the zfh1 enhancer, and that this activator complex is necessary for bringing about zfh1 transcription in these PCs. Finally, a third, Notch-independent mechanism activates zfh1 transcription in the remaining, even skipped-expressing, PCs. Collectively, our data show how the same feature, enrichment of Su(H) binding sites in PC-specific gene enhancers, is utilized by two very distinct mechanisms, one permissive, the other instructive, to contribute to the same overall goal: the specification and differentiation of a cardiac cell subtype by activation of the pericardial gene program. Furthermore, our results demonstrate that the zfh1 enhancer drives expression in two different domains using distinct Notch-instructive and Notch-independent mechanisms.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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