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ECB-ART-44721
Dev Biol 2016 Aug 01;4161:173-186. doi: 10.1016/j.ydbio.2016.05.026.
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An Elk transcription factor is required for Runx-dependent survival signaling in the sea urchin embryo.

Rizzo F , Coffman JA , Arnone MI .


Abstract
Elk proteins are Ets family transcription factors that regulate cell proliferation, survival, and differentiation in response to ERK (extracellular-signal regulated kinase)-mediated phosphorylation. Here we report the embryonic expression and function of Sp-Elk, the single Elk gene of the sea urchin Strongylocentrotus purpuratus. Sp-Elk is zygotically expressed throughout the embryo beginning at late cleavage stage, with peak expression occurring at blastula stage. Morpholino antisense-mediated knockdown of Sp-Elk causes blastula-stage developmental arrest and embryo disintegration due to apoptosis, a phenotype that is rescued by wild-type Elk mRNA. Development is also rescued by Elk mRNA encoding a serine to aspartic acid substitution (S402D) that mimics ERK-mediated phosphorylation of a conserved site that enhances DNA binding, but not by Elk mRNA encoding an alanine substitution at the same site (S402A). This demonstrates both that the apoptotic phenotype of the morphants is specifically caused by Elk depletion, and that phosphorylation of serine 402 of Sp-Elk is critical for its anti-apoptotic function. Knockdown of Sp-Elk results in under-expression of several regulatory genes involved in cell fate specification, cell cycle control, and survival signaling, including the transcriptional regulator Sp-Runt-1 and its target Sp-PKC1, both of which were shown previously to be required for cell survival during embryogenesis. Both Sp-Runt-1 and Sp-PKC1 have sequences upstream of their transcription start sites that specifically bind Sp-Elk. These results indicate that Sp-Elk is the signal-dependent activator of a feed-forward gene regulatory circuit, consisting also of Sp-Runt-1 and Sp-PKC1, which actively suppresses apoptosis in the early embryo.

PubMed ID: 27235147
PMC ID: PMC4961547
Article link: Dev Biol
Grant support: [+]

Genes referenced: elk1 LOC100887844 LOC115919910 LOC588990 runx2
Antibodies: elk1 Ab2
Morpholinos: elk1 MO1

References [+] :
Aktipis, Cancer across the tree of life: cooperation and cheating in multicellularity. 2015, Pubmed