Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ZNF516 Is a Potent Suppressor of the EGFR Oncogene through Chromatin Targeting of the CtBP/LSD1/CoREST Complex

ABSTRACT: In this study, we report that ZNF516 functions as a transcription repressor. We showed that ZNF516 is physically associated with the CtBP/LSD1/CoREST corepressor complex and transcriptionally represses the expression of a collection of genes including EGFR that are critically involved in cell proliferation and motility. We demonstrated that the ZNF516 inhibits the proliferation and invasive potential of breast cancer cells in vitro and suppresses breast cancer growth and metastasis in vivo. We explored the clinical significance of the ZNF516-CtBP/LSD1/CoREST-EGFR axis in breast carcinomas.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97962 | GEO | 2017/05/01

SECONDARY ACCESSION(S): PRJNA383489

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of pituitary glands from wild type and LSD1 knock-out mice

Project description:Precise control of transcriptional programs underlying metazoan development is modulated by enzymatically active co-regulatory complexes, coupled with epigenetic strategies, but how specific members of histone modification enzyme families such as histone methyltransferases and demethylases are utilized in vivo to simultaneously orchestrate distinct developmental gene activation and repression programs remains unclear. Here, we report that the initially-described histone lysine demethylase, LSD1, a component of the CoREST/CtBP corepressor complex, is required for late cell-lineage determination and differentiation during pituitary organogenesis. Surprisingly, LSD1 acts primarily on target gene activation programs, as well as in gene repression programs, based on recruitment of distinct LSD1-containing coactivator or corepressor complexes. Intriguingly, LSD1-dependent gene repression programs can be extended late in development with the induced expression of ZEB1, a Kr.pple-like repressor that can act as a molecular beacon for recruitment of the LSD1-containing CtBP/CoREST corepressor complex, causing repression of an additional cohort of genes, such as GH, that previously required LSD1 for activation.

2007-02-13 | E-TABM-223 | biostudies-arrayexpress

OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis [ChIP-seq]

Project description:Genomic amplification of OTUD7B is frequently found across human cancers. But its role in tumorigenesis is poorly understood. Lysine‐specific demethylase 1 (LSD1) is known to execute epigenetic regulation by forming corepressor complex with CoREST/histone deacetylases (HDACs). However, the molecular mechanisms by which cells maintain LSD1/CoREST complex integrity are unknown. Here, it is reported that LSD1 protein undergoes K63‐linked polyubiquitination. OTUD7B is responsible for LSD1 deubiquitination at K226/277 residues, resulting in dynamic control of LSD1 binding partner specificity and cellular homeostasis. OTUD7B deficiency increases K63‐linked ubiquitination of LSD1, which disrupts LSD1/CoREST complex formation and targets LSD1 for p62‐mediated proteolysis. Consequently, OTUD7B deficiency impairs genome‐wide LSD1 occupancy and enhances the methylation of H3K4/H3K9, therefore profoundly impacting global gene expression and abrogating breast cancer metastasis. Moreover, physiological fluctuation of OTUD7B modulates cell cycle‐dependent LSD1 oscillation, ensuring the G1/S transition. Both OTUD7B and LSD1 proteins are overpresented in high‐grade or metastatic human breast cancer, while dysregulation of either protein is associated with poor survival and metastasis. Thus, OTUD7B plays a unique partner‐switching role in maintaining the integrity of LSD1/CoREST corepressor complex, LSD1 turnover, and breast cancer metastasis.

2021-04-20 | GSE172369 | GEO

OTUD7B Deubiquitinates LSD1 to Govern Its Binding Partner Specificity, Homeostasis, and Breast Cancer Metastasis [RNA-seq]

2021-04-20 | GSE172370 | GEO

Endocrine resistance and breast cancer plasticity are controlled by CoREST

Project description:Using a new model system to track evolution of resistance from ER+ to ER-, we show that the LSD1/CoREST complex is a key determinant for luminal-to-basal reprogramming independently on LSD1’s enzymatic activity.

2022-08-01 | GSE168644 | GEO

Proximity-dependent biotin identification (BioID) reveals a dynamic LSD1-CoREST interactome during embryonic stem cell differentiation

Project description:Lysine specific demethylase 1 (LSD1/KDM1A) regulates gene expression as part of the CoREST complex, along with co-repressor of REST (CoREST) and histone deacetylase 1 (HDAC1). CoREST is recruited to specific genomic loci by components of the core complex and numerous transient interactions with chromatin associated factors and transcription factors. To sample the chromatin environment in proximity to CoREST, we performed proximity-dependent biotin-identification (BioID) with four different members of the complex in 293T cells. Retaining only targets identified with 3 out of 4 baits, we identified 302 CoREST-associated proteins. Among this group were 16 of 18 known CoREST components and numerous novel associations, including readers (CHD3, 4, 6, 7 and 8), writers (KMT2B and KMT2D) and erasers (KDM2B) of histone methylation. However, components of other HDAC1 containing complexes (e.g. Sin3A, NuRD) were largely absent, suggesting that CoREST functions independently. As LSD1 plays an essential role in early embryonic development, we performed BioID using the endogeneously tagged protein in pluripotent, early- and late-differentiating embryonic stem cells. We identified 157 LSD1-associated proteins of which 66 were constitutively associated across all three time-points (44%), including novel interactions with the MMB and ChAHP complexes. These data imply that the majority of CoREST interactions are dynamic and highly cell type dependent.

2021-11-03 | PXD017344 | Pride

Genome-wide maps of CtBP binding profile in breast cancer cell line MCF-7

Project description:CtBP is a global co-repressor by serving as transcriptional factor in multiple pathways. CtBP functioned as transcriptional factor by recruiting other cofactors such as G9a, HDAC1 and PcG proteins. CtBP is found to be over enriched in several type of tumor samples. To dipict the role of CtBP in globally regulating gene expression, we applied ChIP-seq technology to find out the binding profile of CtBP in breast cancer cell line MCF-7. Our data suggest CtBP plays a global regulatory role in DNA damage repair, tumor initiation, and EMT process. Examine CtBP binding in MCF-7 cells

2013-03-20 | E-GEOD-36546 | biostudies-arrayexpress

Genome-wide maps of CtBP binding profile in breast cancer cell line MCF-7

2013-03-20 | GSE36546 | GEO

Expression data from CtBP knockdown MCF-7 cells

Project description:CtBP is a global co-repressor by serving as transcriptional factor in multiple pathways. CtBP functioned as transcriptional factor by recruiting other cofactors such as G9a, HDAC1 and PcG proteins. CtBP is found to be over enriched in several type of tumor samples. To dipict the role of CtBP in globally regulating gene expression, we applied gene microarray technology to find out what subgroups of genes are mainly affected. 6 MCF-7 cell samples, 3 with CtBP knockdown and 3 with control knock down.

2013-03-20 | E-GEOD-36529 | biostudies-arrayexpress

LSD1 functions through CoREST to maternally reprogram histone methylation

Project description:LSD1 functions through CoREST to maternally reprogram histone methylation

| PRJNA705990 | ENA

Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

Project description:Lysine Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4), but has coactivator function on some genes through unclear mechanisms. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and has a distinct AR-linked coactivator function mediated by demethylation of other substrates. Determine the role of LSD1 in androgen signaling.

2014-12-12 | E-GEOD-52201 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data