Quantitating transcription factor redundancy: The relative roles of the ELT-2 and ELT-7 GATA factors in the C. elegans endoderm
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ABSTRACT:
PROVIDER: PRJNA419208 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6309960.fastq.gz | Fastqsanger.gz | |||
| SRR6309970.fastq.gz | Fastqsanger.gz | |||
| SRR6309961.fastq.gz | Fastqsanger.gz | |||
| SRR6309971.fastq.gz | Fastqsanger.gz | |||
| SRR6309962.fastq.gz | Fastqsanger.gz |
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Project description:Two GATA transcription factors, ELT-2 and ELT-7, function in the differentiation of the Caenorhabditis elegans intestine. Though loss of elt-7 causes no discernable phenotype on its own, it significantly enhances intestinal morphology defects in elt-2 loss-of-function mutants. We sought to identify the cohorts of gene targets unique to or shared by ELT-2 and ELT-7 in an effort to determine the logic underlying their differential impact on intestinal development.
2018-02-22 | GSE107175 | GEO
Project description: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.
| S-EPMC6476323 | biostudies-literature
Project description:We identified genome-wide sites of occupancy for the intestine-specific transcription factor ELT-2 in L3-staged N2 worm by performing ELT-2 ChIP-seq on whole worms; we performed RNA-seq on L3-staged N2 whole worms To identify DNA regions of direct ELT-2 occupancy, we performed the following ChIP-seq assays 1) ELT-2 ChIP-seq on L3 staged N2 C. elegans worms; 2) H3K4me3 ChIP-seq on matched L3 staged N2 worms; 3) Mock IgG-only ChIP-seq negative control on L3 stage N2 worms. Input DNA was also sequenced for each replicate. In addition, we performed RNA-seq on two replicates of L3 N2 C. elegans worms.
2016-03-30 | E-GEOD-71720 | biostudies-arrayexpress
Project description:We identified genome-wide sites of occupancy for the intestine-specific transcription factor ELT-2 in L3-staged N2 worm by performing ELT-2 ChIP-seq on whole worms; we performed RNA-seq on L3-staged N2 whole worms
2016-03-30 | GSE71720 | GEO
Project description:During mammalian pre-implantation development, the cells of the blastocyst’s inner cell mass differentiate into the epiblast and primitive endoderm lineages, which give rise to the fetus and extra-embryonic tissues, respectively. Extra-embryonic endoderm differentiation can be modeled in vitro by induced expression of GATA transcription factors in mouse embryonic stem cells. Here we use this GATA-inducible system to quantitatively monitor the dynamics of global proteomic changes during the early stages of this differentiation event and also investigate the fully differentiated phenotype, as represented by embryo-derived extra-embryonic endoderm (XEN) cells. Using mass spectrometry-based quantitative proteomic profiling with multivariate data analysis tools, we reproducibly quantified 2,336 proteins across three biological replicates and have identified clusters of proteins characterized by distinct, dynamic temporal abundance profiles. We first used this approach to highlight novel marker candidates of the pluripotent state and extra-embryonic endoderm differentiation. Through functional annotation enrichment analysis, we have shown that the downregulation of chromatin-modifying enzymes, the re-organization of membrane trafficking machinery and the breakdown of cell-cell adhesion are successive steps of the extra-embryonic differentiation process. Thus, applying a range of sophisticated clustering approaches to a time-resolved proteomic dataset has allowed the elucidation of complex biological processes which characterize stem cell differentiation and could establish a general paradigm for the investigation of these processes.
2015-06-13 | PXD001901 | Pride
Project description:GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of GATA3 with paralog GATA2 in trophoblast progenitors ensures the successful progression of both pre and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either one alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem vs. differentiated trophoblast fate. Also, in trophoblast progenitors GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.
2017-01-25 | GSE92287 | GEO
Project description:GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of GATA3 with paralog GATA2 in trophoblast progenitors ensures the successful progression of both pre and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either one alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem vs. differentiated trophoblast fate. Also, in trophoblast progenitors GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.
2017-01-25 | GSE92292 | GEO
Project description:Chickarmane2008 - Stem cell lineage - NANOG GATA-6 switch
In this work, a dynamical model of lineage
determination based upon a minimal circuit, as discussed in PMID: 17215298
, which contains the Oct4/Sox2/Nanog core as well its interaction
with a few other key genes is discussed.
This model is described in the article:
A computational model for understanding stem cell, trophectoderm and endoderm lineage determination.
Chickarmane V, Peterson C
PloS one. 2008, 3(10):e3478
Abstract:
BACKGROUND: Recent studies have associated the transcription factors, Oct4, Sox2 and Nanog as parts of a self-regulating network which is responsible for maintaining embryonic stem cell properties: self renewal and pluripotency. In addition, mutual antagonism between two of these and other master regulators have been shown to regulate lineage determination. In particular, an excess of Cdx2 over Oct4 determines the trophectoderm lineage whereas an excess of Gata-6 over Nanog determines differentiation into the endoderm lineage. Also, under/over-expression studies of the master regulator Oct4 have revealed that some self-renewal/pluripotency as well as differentiation genes are expressed in a biphasic manner with respect to the concentration of Oct4. METHODOLOGY/
PRINCIPAL FINDINGS: We construct a dynamical model of a minimalistic network, extracted from ChIP-on-chip and microarray data as well as literature studies. The model is based upon differential equations and makes two plausible assumptions; activation of Gata-6 by Oct4 and repression of Nanog by an Oct4-Gata-6 heterodimer. With these assumptions, the results of simulations successfully describe the biphasic behavior as well as lineage commitment. The model also predicts that reprogramming the network from a differentiated state, in particular the endoderm state, into a stem cell state, is best achieved by over-expressing Nanog, rather than by suppression of differentiation genes such as Gata-6.
CONCLUSIONS: The computational model provides a mechanistic understanding of how different lineages arise from the dynamics of the underlying regulatory network. It provides a framework to explore strategies of reprogramming a cell from a differentiated state to a stem cell state through directed perturbations. Such an approach is highly relevant to regenerative medicine since it allows for a rapid search over the host of possibilities for reprogramming to a stem cell state.
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2024-09-02 | BIOMD0000000210 | BioModels
Project description:We discovered enhancers that control GATA-2 expression during mouse development and in adult and generated mutant mouse strains that lack these enhancers, and these mice have very specific and important phenotypes that revealed GATA-2 mechanisms to control stem and progenitor cell transitions. In this study we aim to determine what proteins are under control of the GATA-2 -77 enhancer in a pool of heterogeneous blood progenitor cells with the specific focus on Socs2 expression.
2020-06-05 | PXD013855 | Pride
Project description:Genetic Redundancy of GATA Factors in Extraembryonic Trophoblast Lineage Ensures Progression of both Pre and Postimplantation Mammalian Development
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