This SuperSeries is composed of the SubSeries listed below.
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Specimen part, Cell line
View SamplesSelf-renewal of embryonic stem cells (ESCs) cultured in serum-LIF is incomplete with some cells initiating differentiation. While this is reflected in heterogeneous expression of naive pluripotency transcription factors (TFs), the link between TF heterogeneity and differentiation is not fully understood. Here we purify ESCs with distinct TF expression levels from serum-LIF cultures to uncover early events during commitment from nave pluripotency. ESCs carrying fluorescent Nanog and Esrrb reporters show Esrrb downregulation only in NANOGlow cells. Independent Esrrb reporter lines demonstrate that ESRRBnegative ESCs cannot effectively self-renew. Upon ESRRB loss, pre-implantation pluripotency gene expression collapses. ChIP-Seq identifies different regulatory element classes that bind both OCT4 and NANOG in ESRRBhigh cells. Class I elements lose NANOG and OCT4 binding in ESRRBnegative ESCs and associate with genes expressed preferentially in nave ESCs. In contrast, class II elements retain OCT4 but not NANOG binding in ESRRBnegative cells and associate with more broadly expressed genes. Therefore, mechanistic differences in TF function act cumulatively to restrict potency during exit from nave pluripotency.
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.
Specimen part, Cell line
View SamplesA multilayered transcription regulatory system is unveiled, where protein- and RNA-based repressors are super-imposed in combinatorial fashion to govern the timely triggering of an essential step of erythropoiesis
A KRAB/KAP1-miRNA cascade regulates erythropoiesis through stage-specific control of mitophagy.
Specimen part
View SamplesRNA-seq and expression profile of WT and ZFP57 KO ES cells Overall design: RNA was extracted from both cell lines, PolyA RNA were extracted and RNA-seq was performed
In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
KAP1 regulates gene networks controlling T-cell development and responsiveness.
Specimen part
View SamplesThe modulation of chromatin status at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by KAP1, the universal cofactor of KRAB-containing Zinc Finger Proteins (KRAB-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1 knockout mice displayed a significant expansion of immature thymocytes and imbalances in the ratios of mature T cells in the thymus and the spleen, with impaired responses to TCR stimulation. Transcriptome and chromatin studies revealed that KAP1 directly controls the expression of a number of genes involved in TCR and cytokine signalling, among which Traf1 and FoxO1, and is strongly associated with cis-acting regulatory elements marked by the H3K9me3 repressive mark on the genome of thymic T cells. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB/ZFPs are selectively expressed in T lymphoid cells. These results reveal the so far unsuspected yet important role of KRAB/KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation.
KAP1 regulates gene networks controlling T-cell development and responsiveness.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.
Specimen part
View SamplesChromatin remodeling is fundamental for B cell differentiation. Here, we explored the role in this process of KAP1, the cofactor of KRAB-ZFP transcriptional repressors. B lymphoid-specific Kap1 knockout mice displayed reduced numbers of mature B cells, lower steady-state levels of antibodies and accelerated rates of decay of neutralizing antibodies following viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an upregulation of PTEN, the enzymatic counter-actor of PIK3 signaling, and of genes encoding DNA damage response factors, cell-cycle regulators and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to a number of these genes, and controlled chromatin status at their promoters. Genome-wide, KAP1-binding sites avoided active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. This work thus reveals the role of KRAB/KAP1-mediated epigenetic regulation in B cell development and homeostasis.
KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer.
Cell line, Treatment
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