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The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity [ChIP-seq]

ABSTRACT: The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity [ChIP-seq]

PROVIDER: PRJNA837890 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19193866.fastq.gz	Fastqsanger.gz
	SRR19193867.fastq.gz	Fastqsanger.gz
	SRR19193868.fastq.gz	Fastqsanger.gz
	SRR19193869.fastq.gz	Fastqsanger.gz

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The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity [RNA-seq]

Project description:Eya1 is critical for specifying and maintaining nephron progenitor cells (NPCs). It belongs to a protein family known as phosphatase-transcriptional activator but without intrinsic DNA-binding activity. However, the Eya1-centered network and the spectrum of its interaction partners are underexplored. Here, we combined transcriptomic, genomic and proteomic approaches to characterize gene regulation by Eya1 in the NPCs. We identified Eya1 target genes, genomic binding sites, and partner proteins. Eya1 binds preferentially to promoter sequences and interacts with general transcription factors (TFs), RNA polymerases, different types of TFs, and DNA replication/repair proteins. Intriguingly, we identified REST-binding motifs in 76% of Eya1-binding sites without H3K27ac-deposition, which were present in many Eya1 target genes upregulated in Eya1-deficient NPCs. Eya1 copurified REST-interacting proteins, including chromatin-remodeling factors with ATPase or helicase activity, histone deacetylase/lysine demethylase, and corepressors. Coimmunoprecipitation validated complex formation between Eya1, Hdac1 and Cdyl in kidneys. Thus, these results suggest that through interactions with chromatin-remodeling factors, Eya1 may modify chromatin structure to facilitate the assembly of regulatory complexes that regulate transcription positively or negatively. These findings provide a mechanistic basis for how Eya1 functions as a multifunction protein by cooperating with protein partners in various fundamental biological processes to maintain the cellular state of NPCs.

2022-10-19 | GSE202956 | GEO

The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity [ChIP-seq]

2022-10-19 | GSE202955 | GEO

The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity

Project description:The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity

| PRJNA837882 | ENA

The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity [RNA-seq]

| PRJNA837889 | ENA

Chromatin remodelers interact with Eya1 and Six2 to control nephron progenitor cell self-renewal maintenance

Project description:Eya1 interacts with Six1/2 to induce nephron fate and promote nephron progenitor self-renewal. Haploinsufficiency for these genes in humans causes kidney agenesis or hypoplasia. However, how the Eya1-centered network operates remains elusive. Here we identify Eya1's interacting factors via mass-spectrometry and show that Eya1 and Six2 interact with Brg1-based SWI/SNF chromatin-remodeling complex in the kidney. Depletion of Brg1 results in lack of metanephric mesenchyme and depletion of nephron progenitor cells, which is linked to loss of Eya1 expression. Transcriptional profiling reveals conspicuous downregulation of the proto-oncogene Pbx1 and the Dchs1/Fat4 signaling but premature upregulation of a large subset of genes for podocyte lineages and aberrant activation of oncogenic factors in Brg1-deficent cell. ChIP-seq identifies Brg1-occupancy to enhancers at Pbx1 to a distal enhancer of Eya1 that drives nephron progenitor-specific expression. We demonstrate Six2-dependent Brg1 enrichment to the proximal-promoter of Mycn and two distal enhancers of Pbx1, all of which govern nephron progenitor-specific expression in response to binding to Six2. Together, our results suggest a possible mechanism through which the functional specificity of Brg1-BAFs and Eya1-Six2 in cell cycle regulation and self-renewal of the nephron progenitors may be in part achieved.

2021-10-01 | GSE185050 | GEO

SWI/SNF chromatin remodelers target enhancers via interaction with Eya1 and Six2 to specify metanephric fate and maintain nephron progenitor pool

Project description:Eya1 is a critical regulator for establishing nephron fate and acts upstream of Six2. However, how Eya1-centered network operates remains elusive. Here we identified Eya1's interacting factors via mass-spectrometry and show that Eya1 and Six2 interact with Brg1-based SWI/SNF chromatin-remodeling complex in the kidney. Brg1 specifies the nephron fate and regulates Eya1 expression through binding to multiple cis-regulatory-elements. In the nephron-progenitors, Brg1/Six2 co-occupy cis-regulatory-elements at key loci and Brg1-recruitment to many of these regions is disrupted in the absence of Six2. We demonstrate Six2-dependent Brg1-occupancy to Mycn promoter and two distal enhancers of Pbx1, all of which direct nephron-progenitor-specific expression in response to binding to Six2. RNA-seq analysis reveals that depletion of Brg1 leads to upregulation of genes for podocyte-lineages and aberrant activation of cell-death inducing factors. Together, this study highlights an essential function of the Brg1-BAFs in cooperation with Eya1/Six2 in enhancer-mediated regulation of gene expression in the nephron-progenitors.

2023-10-12 | GSE159483 | GEO

The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and REST-binding sequences to maintain nephron progenitor identity.

Project description:Eya1 is critical for establishing and maintaining nephron progenitor cells (NPCs). It belongs to a family of proteins called phosphatase-transcriptional activators but without intrinsic DNA-binding activity. However, the spectrum of the Eya1-centered networks is underexplored. Here, we combined transcriptomic, genomic and proteomic approaches to characterize gene regulation by Eya1 in the NPCs. We identified Eya1 target genes, associated cis-regulatory elements and partner proteins. Eya1 preferentially occupies promoter sequences and interacts with general transcription factors (TFs), RNA polymerases, different types of TFs, chromatin-remodeling factors with ATPase or helicase activity, and DNA replication/repair proteins. Intriguingly, we identified REST-binding motifs in 76% of Eya1-occupied sites without H3K27ac-deposition, which were present in many Eya1 target genes upregulated in Eya1-deficient NPCs. Eya1 copurified REST-interacting chromatin-remodeling factors, histone deacetylase/lysine demethylase, and corepressors. Coimmunoprecipitation validated physical interaction between Eya1 and Rest/Hdac1/Cdyl/Hltf in the kidneys. Collectively, our results suggest that through interactions with chromatin-remodeling factors and specialized DNA-binding proteins, Eya1 may modify chromatin structure to facilitate the assembly of regulatory complexes that regulate transcription positively or negatively. These findings provide a mechanistic basis for how Eya1 exerts its activity by forming unique multiprotein complexes in various biological processes to maintain the cellular state of NPCs.

| S-EPMC9561260 | biostudies-literature

The transcriptional coactivator Eya1 exerts transcriptional repressive activity by interacting with REST corepressors and DNA recognition sequences to maintain nephron progenitor identity

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-19 | GSE202957 | GEO

Inducible three-factor direct reprogramming to nephron progenitors using piggyBac transposons

Project description:All nephrons in the mammalian kidney arise from a transient nephron progenitor population that is lost after birth. The recreation of nephron progenitors (NPs) and/or their maintenance in culture has been a major focus of renal regenerative strategies. Using a lentiviral screening approach, we previously generated an induced nephron progenitor (iNP) state in vitro using a pool of six transcription factors (SIX1, SIX2, HOXA11, OSR1, EYA1, SNAI2). Here, using an inducible piggyBac transposon system, we demonstrate efficient reprogramming to iNPs with only three transcription factors (SNAI2, EYA1 and SIX1). Coupled with maintenance in culture conditions supportive of this progenitor state, the resulting population can contribute to developing nephrons in vitro, ex vivo and in vivo. This approach provides a rapid and efficient method for the generation of NPs from human somatic cells.

2019-11-28 | GSE107410 | GEO

Chromatin remodelers interact with Eya1 and Six2 to control nephron progenitor cell self-renewal maintenance

Project description:Chromatin remodelers interact with Eya1 and Six2 to control nephron progenitor cell self-renewal maintenance

| PRJNA767478 | ENA