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Analysis of gene expression profiles in primary embryonic fibroblasts deficient for the Ing1 locus

ABSTRACT: The ING familiy of tumor suppressor proteins control several cellular functions relevant to anti-tumor protection, like cell-cycle control, apoptosis, senescence or migration. ING proteins are functionally linked to the p53 pathway, and they participate in transcriptional control via the recognition of histone marks and recruitment of protein complexes with chromatin-modifying activity to specific promoters. Here, we have investigated the global impact of ING1 in gene regulation through genome-wide analysis of expression profiles in primary embryonic fibroblasts deficient for the Ing1 locus. We find that Ing1 has a predominant role as transcriptional repressor in this setting, affecting the expression of genes involved in a variety of cellular functions. Within the subset of genes showing differential expression, we have identified DGCR8, a protein involved in the early steps of microRNA biogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE18519 | GEO | 2010/10/01

SECONDARY ACCESSION(S): PRJNA120191

REPOSITORIES: GEO

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Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1

Project description:The ING familiy of tumor suppressor proteins control several cellular functions relevant to anti-tumor protection, like cell-cycle control, apoptosis, senescence or migration. ING proteins are functionally linked to the p53 pathway, and they participate in transcriptional control via the recognisition of histone marks and recruitment of protein complexes with chromatin-modifying activity to specific promoters. Here, we have investigated the global impact of ING1 in gene regulation through genome-wide analysis of expression profiles in primary embryonic fibroblasts deficient for the Ing1 locus. We find that Ing1 has a predominant role as transcriptional repressor in this setting, affecting the expression of genes involved in a variety of cellular functions. Within the subset of genes showing differential expression, we have identified DGCR8, a protein involved in the early steps of microRNA biogenesis. We show that ING1 binds to the DGCR8 promoter and controls its transcription through chromatin regulation at its promoter. We also find that ING1 and DGCR8 can cooperate in restraining proliferation. In summary, this study reveals a novel connection between ING1 and a regulator of microRNA biogenesis, and identifies new links between tumor suppressor proteins and the microRNA machinery For MEFs, two replicates were used for each genotype (wild-type or Ing1-deficient). Wild type MEFs were used as reference. For EMG cells [a cell line generated in our laboratory], two replicates were used for each condition (cells where ING1 was induced by doxycycline or uninduced cells). Uninduced cells were used as reference.

2010-06-20 | E-GEOD-18645 | biostudies-arrayexpress

Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1

2009-10-21 | GSE18645 | GEO

Analysis of gene expression profiles in primary embryonic fibroblasts deficient for the Ing1 locus

Project description:The ING familiy of tumor suppressor proteins control several cellular functions relevant to anti-tumor protection, like cell-cycle control, apoptosis, senescence or migration. ING proteins are functionally linked to the p53 pathway, and they participate in transcriptional control via the recognition of histone marks and recruitment of protein complexes with chromatin-modifying activity to specific promoters. Here, we have investigated the global impact of ING1 in gene regulation through genome-wide analysis of expression profiles in primary embryonic fibroblasts deficient for the Ing1 locus. We find that Ing1 has a predominant role as transcriptional repressor in this setting, affecting the expression of genes involved in a variety of cellular functions. Within the subset of genes showing differential expression, we have identified DGCR8, a protein involved in the early steps of microRNA biogenesis. In this study we have taken an unbiased approach to identify Ing1 targets, consisting in the comparison of expression profiles by genome-wide microarray analysis (Codelink mouse whole-genome expression microarrays), of mouse embryonic fibroblasts from embryos with the Ing1 locus inactivated by the insertion of a gene trap cassette, and their wild-type littermates. Three biological replicates were done for each phenotype.

2010-10-01 | E-GEOD-18519 | biostudies-arrayexpress

Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1

Project description:Regulation of the microRNA processor DGCR8 by the tumor suppressor ING1

| PRJNA121579 | ENA

CG7379/ING1 in cancer progression. A study of migration and invasion in in vivo and in vitro epithelial systems

Project description:Metastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. A large-scale genetic screen was carried out to identify genes that affect tumour progression in the living fly. This screen identified CG7379 as promoting cancer cell invasion when gene expression was knocked down in epithelial tumours in the dorsal thorax of the fly. The uncharacterised CG7379 Drosophila gene shows high homology with the human ING (inhibitor of growth) gene family. ING proteins are known to be involved in the control of cell proliferation, senescence and apoptosis. However, their potential role in cell migration and invasion is yet to be properly documented. Homeostasis of epithelial tissues relies on the control of cell polarity and architecture, and our results strongly suggest that CG7379 and ING1 play an important role in cell-cell junction integrity maintenance. The knockdown of both the Drosophila and human gene increases invasion in the living animal and in in vitro invasion assays respectively and gene knock-down led to severe disruption of cell-cell junction integrity. We used Clariom™ S Assay arrays to detail the global programme of gene expression following ING1 KD to detect DEG involved in regulation of cell motility and cell-cell junction assembly and maintenance.

2021-09-22 | GSE125438 | GEO

Gene expression changes in mouse embryonic fibroblasts (MEF cells) deficient for Ing1 and Gadd45a

Project description:ING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We found that ING1b and GADD45a physically and functionally interact in the epigenetic regulation of specific target genes. In order to study this interaction further, we analysed the transcriptional changes in MEF cells from single and double Ing1/Gadd45 knockout mice via microarray profiling. Mouse embryonic fibroblasts (MEF cells) were isolated from embryonic day E15.5 male embryos, either wild-type (WT) or knockout for Ing1 (Ing1-/-), Gadd45a (Gadd45a-/-) or Ing1/Gadd45a (double knockout, DKO), and cultured for 3 passages. Samples were then collected in duplicates per MEF line for expression array profiling.

2013-02-04 | E-GEOD-43318 | biostudies-arrayexpress

Gene expression changes in white adipose tissue from Ing1- and Gadd45a- single- or double-knockout mice

Project description:ING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We previously found that ING1b is essential to target GADD45a-mediated active DNA-demethylation via TET1 to specific loci. Hence, GADD45a and ING1 play a crucial role in epigenetic gene regulation. In order to study the physiological role of ING1-GADD45a on gene expression regulation, we compared the expression profiles of white adipose tissue (WAT) from wildtype, Ing1-/-, Gadd45-/- and double-knockout (DKO) mice.

2018-06-11 | GSE99605 | GEO

Gene expression changes in Ing1- and Gadd45a- single- or double-knockout mouse embryonic fibroblasts

Project description:ING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We previously found that ING1b is required to target GADD45a-mediated active DNA-demethylation via TET1 to specific loci. In order to study the impact of ING1-GADD45a on gene expression, we compared the expression profile of wildtype mouse embryonic fibroblasts (MEFs) with Ing1- and Gadd45a- single- or double-knockout (DKO) MEFs.

2018-06-11 | GSE115187 | GEO

ING1 ChIP-Seq in mouse embryonic fibroblasts

Project description:ING1b is a nuclear protein involved in the regulation of cell growth, apoptosis and DNA repair. Importantly, we previously found that ING1 is implicated in epigenetic gene regulation and required for targeting GADD45a-mediated active DNA demethylation via TET1. In this study, we identified ING1 bound genomic regions in mouse embryonic fibroblasts (MEFs) via ChIP-Sequencing.

2018-06-11 | GSE99603 | GEO

Whole genome bisulfite sequencing of Ing1/Gadd45a double knockout and wildtype mouse embryonic fibroblasts

Project description:ING1b and GADD45a are nuclear proteins involved in the regulation of cell growth, apoptosis and DNA repair. We previously found that ING1b is essential to target GADD45a-mediated active DNA-demethylation via TET1 to specific loci. In order to study the physiological impact of ING1-GADD45a on DNA methylation in base-resolution genome-wide, we compared the methylation levels of wildtype mouse embryonic fibroblasts (MEFs) with Ing1/Gadd45a double-knockout MEFs via whole genome bisulfite sequencing.

2018-06-11 | GSE99601 | GEO

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