Quantitating transcription factor redundancy: The relative roles of the ELT-2 and ELT-7 GATA factors in the C. elegans endoderm.

TitleQuantitating transcription factor redundancy: The relative roles of the ELT-2 and ELT-7 GATA factors in the C. elegans endoderm.
Publication TypeJournal Article
Year of Publication2018
AuthorsDineen A, Nishimura EOsborne, Goszczynski B, Rothman JH, McGhee JD
JournalDev Biol
Volume435
Issue2
Pagination150-161
Date Published2018 03 15
ISSN1095-564X
KeywordsAnimals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Differentiation, Endoderm, GATA Transcription Factors, Gene Expression Regulation, Developmental, Genes, Helminth, Genes, Reporter, Genetic Association Studies, Intestinal Mucosa, Intestines, Larva, Promoter Regions, Genetic, Transcription, Genetic, Transcriptome
Abstract

The two GATA transcription factors ELT-2 and ELT-7 function in the differentiation of the C. elegans intestine. ELT-2 loss causes lethality. ELT-7 loss causes no obvious phenotype but enhances the elt-2(-) intestinal phenotype. Thus, ELT-2 and ELT-7 appear partially redundant, with ELT-2 being more influential. To investigate the different regulatory roles of ELT-2 and ELT-7, we compared the transcriptional profiles of pure populations of wild-type, elt-2(-), elt-7(-), and elt-7(-); elt-2(-) double mutant L1-stage larvae. Consistent with the mutant phenotypes, loss of ELT-2 had a>25 fold greater influence on the number of significantly altered transcripts compared to the loss of ELT-7; nonetheless, the levels of numerous transcripts changed upon loss of ELT-7 in the elt-2(-) background. The quantitative responses of individual genes revealed a more complicated behaviour than simple redundancy/partial redundancy. In particular, genes expressed only in the intestine showed three distinguishable classes of response in the different mutant backgrounds. One class of genes responded as if ELT-2 is the major transcriptional activator and ELT-7 provides variable compensatory input. For a second class, transcript levels increased upon loss of ELT-2 but decreased upon further loss of ELT-7, suggesting that ELT-7 actually overcompensates for the loss of ELT-2. For a third class, transcript levels also increased upon loss of ELT-2 but remained elevated upon further loss of ELT-7, suggesting overcompensation by some other intestinal transcription factor(s). In spite of its minor loss-of-function phenotype and its limited sequence similarity to ELT-2, ELT-7 expressed under control of the elt-2 promoter is able to rescue elt-2(-) lethality. Indeed, appropriately expressed ELT-7, like appropriately expressed ELT-2, is able to replace all other core GATA factors in the C. elegans endodermal pathway. Overall, this study focuses attention on the quantitative intricacies behind apparent redundancy or partial redundancy of two related transcription factors.

DOI10.1016/j.ydbio.2017.12.023
Alternate JournalDev. Biol.
PubMed ID29360433
PubMed Central IDPMC6476323
Grant ListR01 HD081266 / HD / NICHD NIH HHS / United States
R01 HD082347 / HD / NICHD NIH HHS / United States
R35 GM124877 / GM / NIGMS NIH HHS / United States