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Studying the effects of the TEN1-ICD on transcriptional regulation

ABSTRACT: Teneurins are large type II transmembrane proteins that are necessary for the normal development of the central nervous system (CNS). While many studies highlight the significance of teneurins, especially during development, there is only limited information known about the molecular mechanisms of function. Previous studies have shown that the N-terminal intracellular domain (ICD) of teneurins can be cleaved at the membrane and subsequently translocates to the nucleus where it can influence gene transcription. Target genes as well as mechanisms have yet to be elucidated, and thus we are investigating the transcriptional activity of the human teneurin-1 ICD in this study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE61704 | GEO | 2015/02/04

SECONDARY ACCESSION(S): PRJNA261901

REPOSITORIES: GEO

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Studying the effects of the TEN1-ICD on transcriptional regulation

Project description:Teneurins are large type II transmembrane proteins that are necessary for the normal development of the central nervous system (CNS). While many studies highlight the significance of teneurins, especially during development, there is only limited information known about the molecular mechanisms of function. Previous studies have shown that the N-terminal intracellular domain (ICD) of teneurins can be cleaved at the membrane and subsequently translocates to the nucleus where it can influence gene transcription. Target genes as well as mechanisms have yet to be elucidated, and thus we are investigating the transcriptional activity of the human teneurin-1 ICD in this study. For the whole transcriptome analysis of TEN1-ICD overexpression, we used a modified and improved tet-system. Two separate vectors are required to make the cell line stable. One contains the tet-activating domain fused to a glucocorticoid binding domain (GBD). The other contains the tetO operator sequences directly upstream of a CMV promoter and the gene to be overexpressed. BS149 cells were first transfected with pirtetR-GBD and made stable by Puromycin selection, and then after further transfection with either ptetO-eGFP-His (negative control) or ptetO-TEN1-ICD-eGFP-His by Hygromycin selection. The stable BS149 cell lines were split into three 10 cm Petri dishes each. The triplicate cell lines were cultured once before induction with Dexamethasone and Doxycycline. The overexpressing cells were then FACS-sorted directly into RLT lysis buffer (Qiagen) at a 3:1 volume ratio of lysis buffer to cells in PBS, 24 h post-induction.

2015-02-04 | E-GEOD-61704 | biostudies-arrayexpress

Comparing the effects of MITF on transcriptional regulation to the TEN1-ICD

2015-02-04 | GSE61705 | GEO

Comparing the effects of MITF on transcriptional regulation to the TEN1-ICD

Project description:We identified histidine triad nucleotide binding protein 1 (HINT1) as a human teneurin-1 ICD interaction partner in a yeast-2 hybrid screen. This interaction was confirmed in human cells, where HINT1 is known to inhibit the transcription of target genes by directly binding to transcription factors at the promoter. In a whole transcriptome analysis of BS149 glioblastoma cells overexpressing the teneurin-1 ICD, several microphthalmia-associated transcription factor (MITF) target genes were found to be up-regulated. Interestingly, MITF is one of the transcription factors inhibited by HINT1. Thus, we directly compare the transcriptomes of MITF versus TEN1-ICD overexpressing BS149 cells in this study, in order to reveal any co-regulated genes. For the whole transcriptome analysis of MITF, cells were transiently transfected in triplicates with either, pcDNA3.1-RFP-HA (negative control) or pcDNA3.1-MITF-RFP-HA. The overexpressing cells were then FACS-sorted directly into RLT lysis buffer (Qiagen) at a 3:1 volume ratio of lysis buffer to cells in PBS, 24 h post-transfection.

2015-02-04 | E-GEOD-61705 | biostudies-arrayexpress

Studying the effects of the TEN1-ICD on transcriptional regulation

Project description: Not available

| S-ECPF-GEOD-61704 | biostudies-other

TEN1-ICD studies

Project description:This SuperSeries is composed of the SubSeries listed below.

2015-02-04 | GSE61706 | GEO

TEN1-ICD studies

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

2015-02-04 | E-GEOD-61706 | biostudies-arrayexpress

Project description:TEN1-ICD studies

| PRJNA261896 | ENA

Expression data from a mouse small cell lung cancer (SCLC) cell line, KP1, transfected with Notch-ICD

2015-05-21 | GSE69091 | GEO

Expression data from a mouse small cell lung cancer (SCLC) cell line, KP1, transfected with Notch-ICD

Project description:Transient transfection of activated Notch1 (Notch1-ICD) decreases cellular proliferation and reduces the expression of a subset of neuroendocrine genes. We used microarrays to identify the gene expression changes 48 hours after overexpression of Notch1-ICD. mSCLC cells transfected with Notch1-ICD-ires-GFP were FACS sorted for GFP+ cells 48 hours after transfection. RNA was then extracted and hybridized to Affymetrix GeneChip® Mouse Gene 2.0 ST array.

2015-05-21 | E-GEOD-69091 | biostudies-arrayexpress

Genome wide H3K4me2 detection after CD74 activation.

Project description:CD74 (invariant chain), expressed on B cells, is directly involved in shaping the B cell repertoire by regulating their survival in health and disease. Binding of its ligand, macrophage migration inhibitory factor (MIF), induces a cascade that results in CD74 intramembrane proteolysis, and the release of the CD74 intracellular domain (CD74-ICD). CD74-ICD translocates to the nucleus where it induces activation of transcription. In the current study, we characterized the transcription factor activity of CD74-ICD. Following histone modifications we are able to characterize CD74's binding sites as regulatory areas.

2022-11-03 | GSE181676 | GEO

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