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Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during progenitor cell differentiation

ABSTRACT: Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during progenitor cell differentiation

PROVIDER: PRJNA516584 | ENA |

REPOSITORIES: ENA

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Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during progenitor cell differentiation

Project description:Chromatin-associated RNA-Seq of pre-B cell line B3 transduced with Ikaros (Ikaros-ERt2) or Myc (Myc-ERt2) or Ikaros+Myc or control vector (Empty).

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Feedforward regulation of Myc coordinates lineage-specific with housekeeping gene expression during B cell progenitor cell differentiation.

Project description: Not available

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WSB1 regulates c-Myc expression through β-Catenin signalling and forms a feedforward circuit.

Project description:The dysregulation of transcription factors is widely associated with tumourigenesis. As the most well-defined transcription factor in multiple types of cancer, c-Myc can transform cells by transactivating various downstream genes. Given that there is no effective way to directly inhibit c-Myc, c-Myc targeting strategies hold great potential for cancer therapy. In this study, we found that WSB1, which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples, is a direct target gene of c-Myc, and can positively regulate c-Myc expression, which forms a feedforward circuit promoting cancer development. RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted c-Myc expression through the β-Catenin pathway. Mechanistically, WSB1 affected β-Catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptor β-TRCP recruitment, which inhibited the ubiquitination of β-Catenin and transactivated c-Myc. Of interest, the effect of WSB1 on c-Myc was independent of its E3 ligase activity. Moreover, overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumour-driven effect of c-Myc overexpression. Thus, our findings revealed a novel mechanism involved in tumourigenesis in which the WSB1/c-Myc feedforward circuit played an essential role, highlighting a potential c-Myc intervention strategy in cancer treatment.

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Oncogenic MYC Activates a Feedforward Regulatory Loop Promoting Essential Amino Acid Metabolism and Tumorigenesis

Project description:Oncogenic MYC Activates a Feedforward Regulatory Loop Promoting Essential Amino Acid Metabolism and Tumorigenesis

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Oncogenic MYC Activates a Feedforward Regulatory Loop Promoting Essential Amino Acid Metabolism and Tumorigenesis

Project description:Oncogenic MYC selectively activates Slc7a5 and Slc43a1 transcription and thus promotes essential amino acids (EAAs) uptake in Daudi cells. Elevated EAAs in turn stimulate Myc mRNA translation, prompting us to investigate whether Slc7a5/Slc43a1 inhibition affects MYC-dependent transcription. We performed microarrays to profile global gene expression and to identify Slc7a5-regulated genes.

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Enhancer-core promoter specificity separates developmental and housekeeping regulation

Project description:Gene transcription in animals involves the assembly of the RNA polymerase II complex at core promoters and its cell type-specific activation by genomic enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has remained less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different types of core promoters might exhibit an intrinsic specificity towards certain types of enhancers. Here, we show that thousands of enhancers in D. melanogaster S2 cells and ovarian somatic cells (OSCs) exhibit a marked specificity towards one of two core promoters M-bM-^@M-^S one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor. Enhancers that activate the housekeeping core promoter are functional across the two different cell types, while developmental enhancers exhibit strong cell type specificity. Both enhancer classes differ in their overall genomic distribution, the functions of neighbouring genes,these genesM-bM-^@M-^Y core promoter elements, as well as the associated factors. Our results provide evidence for a sequence-encoded enhancer-core promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome. STARR-seq was performed in S2 and OSC cells using two core promoters each representing housekeeping and developmental transcription programs. Data for housekeeping promoters (hkCP) are presented in this series; Data for developmental core promoters (dCP) samples are presented in GSE40739.

2014-12-10 | E-GEOD-57876 | biostudies-arrayexpress

The base pairing RNA Spot 42 participates in a multi-output feedforward loop to help enact catabolite repression in Escherichia coli

Project description:Bacteria selectively consume some carbon sources over others through a regulatory mechanism termed catabolite repression. Here, we show that the base pairing RNA Spot 42 plays a broad role in catabolite repression in Escherichia coli by directly repressing genes involved in central and secondary metabolism, redox balancing, and the consumption of diverse non-preferred carbon sources. Many of the genes repressed by Spot 42 are transcriptionally activated by the global regulator CRP. Since CRP represses Spot 42, these regulators participate in a specific regulatory circuit called a multi-output feedforward loop. We found that this loop can reduce leaky expression of target genes in the presence of glucose and can maintain repression of target genes under changing nutrient conditions. Our results suggest that base pairing RNAs in feedforward loops can help shape the steady-state levels and dynamics of gene expression. MG1655 lacIq cells harboring the control vector pBRplac or the Spot 42-inducible vector pSpot42 were grown in LB to an ABS600 of ~0.4 and treated with 1 mM IPTG. After 7 min, total RNA was isolated using the hot phenol extraction procedure.

2011-01-01 | E-GEOD-24875 | biostudies-arrayexpress

Enhancer-core promoter specificity separates developmental and housekeeping regulation

Project description:Gene transcription in animals involves the assembly of the RNA polymerase II complex at core promoters and its cell type-specific activation by genomic enhancers that can be located more distally. However, how ubiquitous expression of housekeeping genes is achieved has remained less clear. In particular, it is unknown whether ubiquitously active enhancers exist and how developmental and housekeeping gene regulation is separated. An attractive hypothesis is that different types of core promoters might exhibit an intrinsic specificity towards certain types of enhancers. Here, we show that thousands of enhancers in D. melanogaster S2 cells and ovarian somatic cells (OSCs) exhibit a marked specificity towards one of two core promoters – one derived from a ubiquitously expressed ribosomal protein gene and another from a developmentally regulated transcription factor. Enhancers that activate the housekeeping core promoter are functional across the two different cell types, while developmental enhancers exhibit strong cell type specificity. Both enhancer classes differ in their overall genomic distribution, the functions of neighbouring genes,these genes’ core promoter elements, as well as the associated factors. Our results provide evidence for a sequence-encoded enhancer-core promoter specificity that separates developmental and housekeeping gene regulatory programs for thousands of enhancers and their target genes across the entire genome.

2014-12-10 | GSE57876 | GEO

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