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Transcriptional gene expression regulation in medullary thymic epithelial cells by the transcription factors Ehf, Fezf2, Elf3 and Klf4

ABSTRACT: Transcriptional gene expression regulation in medullary thymic epithelial cells by the transcription factors Ehf, Fezf2, Elf3 and Klf4

PROVIDER: PRJNA973607 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24620835_1.fastq.gz	Fastqsanger.gz
	SRR24620835_2.fastq.gz	Fastqsanger.gz
	SRR24620836_1.fastq.gz	Fastqsanger.gz
	SRR24620836_2.fastq.gz	Fastqsanger.gz
	SRR24620837_1.fastq.gz	Fastqsanger.gz

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Transcriptional gene expression regulation in medullary thymic epithelial cells by the transcription factors Ehf, Fezf2, Elf3 and Klf4

Project description:ChIP sequencing of Ehf, Fezf2, Elf3 and Klf4 was performed on medullary thymic epithelial cells to analyze the role of Ehf-, Fezf2-, Elf3- and Klf4-dependent gene regulation in mTECs.

2024-02-14 | GSE232702 | GEO

Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development.

Project description:Thymic epithelial cells are indispensable for T cell maturation and selection and the induction of central immune tolerance. The self-peptide repertoire expressed by medullary thymic epithelial cells is in part regulated by the transcriptional regulator Aire (Autoimmune regulator) and the transcription factor Fezf2. Due to the high complexity of mTEC maturation stages (i.e., post-Aire, Krt10+ mTECs, and Dclk1+ Tuft mTECs) and the heterogeneity in their gene expression profiles (i.e., mosaic expression patterns), it has been challenging to identify the additional factors complementing the transcriptional regulation. We aimed to identify the transcriptional regulators involved in the regulation of mTEC development and self-peptide expression in an unbiased and genome-wide manner. We used ATAC footprinting analysis as an indirect approach to identify transcription factors involved in the gene expression regulation in mTECs, which we validated by ChIP sequencing. This study identifies Fezf2 as a regulator of the recently described thymic Tuft cells (i.e., Tuft mTECs). Furthermore, we identify that transcriptional regulators of the ELF, ESE, ERF, and PEA3 subfamily of the ETS transcription factor family and members of the Krüppel-like family of transcription factors play a role in the transcriptional regulation of genes involved in late mTEC development and promiscuous gene expression.

| S-EPMC10901246 | biostudies-literature

RNA-seq of postnatal day 0 (P0) wild-type, Fezf2-/- cortices, and Fezf2-/-;Fezf2-EnR cortices

Project description:The goal of the study was to compare gene expression of P0 wild-type, P0 Fezf2-/- cortices, and Fezf2-/-; Fezf2-EnR cortices. Total RNAs were isolated from P0 cortices dissected from wild-type (n=3), Fezf2-/- mice (n=4), and Fezf2-/-; Fezf2-EnR cortices (n=2), following Qiagen RNAeasy kit instruction.Sequence libraries were made following Illumina RNA PolyA library preparation guide.The libaries were pair-end sequenced (150nt per end). Differentially expressed genes were identified by DESEQ.

2021-06-11 | GSE160202 | GEO

Expression data from WT and Fezf2 KO mTECs

Project description:Fezf2 is highly and specifically expressed in mTECs in mouse thymus and Fezf2 deficiency (Fezf2 KO) in the thymus leads to autoimmunity. However, it is unclear how Fezf2 contributes to thymic gene expression. We collected WT and Fezf2 KO mTECs by FACS, and performed microarrays to determine genes regulated by Fezf2. mTECs were subjected to RNA extraction (from WT or Fezf2 KO mTECs) and hybridization on Affymetrix microarrays.

2015-11-05 | E-GEOD-69105 | biostudies-arrayexpress

Expression data from WT and Fezf2 KO mTECs

2015-11-05 | GSE69105 | GEO

Genome-Wide Binding of Ehf in mouse corneal epithelium

Project description:The cornea, composed of epithelium, stroma and endothelium, protects the anterior compartment of the eye from damage and allows transmission of light into the eye. While well described morphologically, no studies have investigated the global gene expression changes in the cornea throughout the mouseM-bM-^@M-^Ys life. We characterized the global gene expression profile of mouse cornea from early development through aging, and compared to gene expression in other epithelial tissue, to identify cornea enriched genes, pathways, and transcriptional regulators. We identified Ehf, an ets family transcription factor, as being highly selectively expressed in the corneal epithelium compared to the stroma, and highly expressed in cornea compared to other epithelial tissues. siRNA experiments and Ehf ChIP-Seq on mouse corneal epithelium confirm the role of this factor in promoting epithelial identity and cell differentiation, and suggest it carries out these functions through interactions with other cornea epithelial differentiation factors including Klf4. Whole eye globes were dissected from wild type CB6 mice. Corneal epithelium was isolated by digestion in 50% EMEM/dispase II with 50 mM sorbitol for two hours at 37M-BM-0C. ChIP was performed with an Ehf antibody, and was sequenced with an input control.

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Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance

Project description:Medullary thymic epithelial cells (mTECs) are essential for the establishment of self-tolerance in T cells. Promiscuous gene expression by a subpopulation of mTECs regulated by nuclear protein Aire contributes to the display of self-genomic products to newly generated T cells. Recent reports have highlighted additional self-antigen-displaying mTEC subpopulations; namely, Fezf2-expressing mTECs and a mosaic of self-mimetic mTECs including thymic tuft cells. In addition, a functionally different subset of mTECs produces chemokine CCL21 that attracts developing thymocytes to the medullary region. Here we report that CCL21+ mTECs and Aire+ mTECs non-redundantly cooperate to direct self-tolerance to prevent autoimmune pathology by optimizing the deletion of self-reactive T cells and the generation of regulatory T cells. We also detected a cooperation for self-tolerance between Aire and Fezf2, which unexpectedly regulates thymic tuft cells. Our results indicate an indispensable interplay among functionally diverse mTECs for the establishment of central self-tolerance.

2024-03-08 | GSE243180 | GEO

ChIP-seq analysis of Fezf2 in mTECs

Project description:To investigate the genome-wide binding pattern of Fezf2, we performed ChIP-seq analysis for Fezf2. ChIP-seq of transcription factor in mTECs is difficult because of small number of mTECs or difficulty in gaining ChIP grade antibodies. Then, we generated Fezf2-3Flag knock in mice and performed ChIP-seq analysis by using anti-Flag antibody.

2020-02-07 | GSE144878 | GEO

Functionally diverse thymic medullary epithelial cells interplay to direct central tolerance II

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