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Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage [ChIP-chip]

ABSTRACT: ING2 (inhibitor of growth family member 2) is a component of a chromatin-regulatory complex that represses gene expression and is implicated in cellular processes that promote tumor suppression. However, few direct genomic targets of ING2 have been identified and the mechanism(s) by which ING2 selectively regulates genes remains unknown. Here we provide evidence that direct association of ING2 with the nuclear phosphoinositide phosphatidylinositol-5-phosphate (PtdIns(5)P) regulates a subset of ING2 targets in response to DNA damage. At these target genes, the binding event between ING2 and PtdIns(5)P is required for ING2 promoter occupancy and ING2-associated gene repression. Moreover, depletion of PtdIns(5)P attenuates ING2-mediated regulation of these targets in the presence of DNA damage. Taken together, these findings support a model in which PtdIns(5)P functions as a sub-nuclear trafficking factor that stabilizes ING2 at discrete genomic sites. FLAG-ING2 ChIP-chip of stably-transduced HT1080 cells in the presence of vehicle (DMSO) or etoposide. Each condition is tested in duplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Dennis Bua

PROVIDER: E-GEOD-47688 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage [expression]

Project description:ING2 (inhibitor of growth family member 2) is a component of a chromatin-regulatory complex that represses gene expression and is implicated in cellular processes that promote tumor suppression. However, few direct genomic targets of ING2 have been identified and the mechanism(s) by which ING2 selectively regulates genes remains unknown. Here we provide evidence that direct association of ING2 with the nuclear phosphoinositide phosphatidylinositol-5-phosphate (PtdIns(5)P) regulates a subset of ING2 targets in response to DNA damage. At these target genes, the binding event between ING2 and PtdIns(5)P is required for ING2 promoter occupancy and ING2-associated gene repression. Moreover, depletion of PtdIns(5)P attenuates ING2-mediated regulation of these targets in the presence of DNA damage. Taken together, these findings support a model in which PtdIns(5)P functions as a sub-nuclear trafficking factor that stabilizes ING2 at discrete genomic sites.

2013-12-31 | GSE47645 | GEO

Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage [ChIP-chip]

2013-12-31 | GSE47688 | GEO

Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage [expression]

2013-12-31 | E-GEOD-47645 | biostudies-arrayexpress

Expression profiling of mouse ing2 -/- mice with spermatogenic arrest and infertility

Project description:Expression profiling of mouse ing2 -/- testis vs WT reveals gene expression differences consistent with spermatogenic arrest and infertility. Ing2 is indispensable for male germ cell development in mice. While mice deficient for Ing2 were born and grew without apparent abnormalities, male, but not female, were infertile, consistent with the highest expression of Ing2 in testes in wild-type mice and in humans. Histological and DNA content analyses in Ing2-/- testes revealed a spermatogenesis arrest at meiotic phase and enhanced apoptosis associated with increased p53, resulting in a decline in mature spermatozoa, which became more severe in older age. HDAC1 accumulation and core histone deacetylation at pachytene stage were impaired in Ing2-/- testes, suggesting that the recruitment of HDAC1 by Ing2 plays a critical role in spermatogenesis. This study establishes Ing2 as a novel mammalian regulator of spermatocyte differentiation, which coordinates spermatogenesis stage-specific histone modifications. This study has implications in understanding human male infertility.

2010-11-19 | GSE18610 | GEO

Nuclear phosphatidylinositol (3,4,5) triphosphate interactome uncovers an enrichment in nucleolar proteins

Project description:Polyphosphoinositides (PPIn) play essential functions as lipid signalling molecules and many of their functions have been elucidated in the cytoplasm. However, PPIns are also intranuclear where they contribute to chromatin remodelling, transcription and mRNA splicing. The PPIn, phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) has been mapped to the nucleus and nucleoli but its role remains unclear in this subcellular compartment. To gain further insights into the nuclear functions of PtdIns(3,4,5)P3, we applied a previously developed quantitative mass spectrometry-based approach to identify the targets of PtdIns(3,4,5)P3 from isolated nuclei. We identified 179 potential PtdIns(3,4,5)P3-interacting proteins and gene ontology analysis for the biological functions of this dataset revealed an enrichment in RNA processing/splicing, cytokinesis, protein folding and DNA repair. Interestingly, about half of these interactors were common to nucleolar protein datasets, some of which had dual functions in rRNA transcription and DNA repair, including Poly(ADP-Ribose) Polymerase 1 (PARP1),. PARP1 was found to interact directly with PPIns and to co-localise with PtdIns(3,4,5)P3 in the nucleolus. Focusing on another factor involved in RNA processing, heterogeneous nuclear ribonucleoprotein U (hnRNPU/SAF-A) was also identified and validated as a direct PPIn-interacting protein. Deletion of the polybasic motif in its DNA binding domain prevented PPIn interaction. In conclusion, the PtdIns(3,4,5)P3 interactome reported here identified several nucleolar proteins and splicing factors and further pointed to roles for this lipid in these processes.

2021-06-28 | PXD020870 | Pride

Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-12-31 | E-GEOD-47689 | biostudies-arrayexpress

Expression profiling of mouse ing2 -/- mice with spermatogenic arrest and infertility

2010-11-19 | E-GEOD-18610 | biostudies-arrayexpress

Project description:Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage

| PRJNA207297 | ENA

Homo sapiens

Project description:Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage [expression]

| PRJNA207300 | ENA

Homo sapiens

Project description:Nuclear phosphatidylinositol-5-phosphate regulates ING2 stability at discrete chromatin targets in response to DNA damage [ChIP-chip]

| PRJNA207299 | ENA

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