Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-49685
PROVIDER: PRJNA214707 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Identification of Myt1 as a subunit of the neural cell type-specific LSD1 complex
2015-07-17 | E-GEOD-49685 | ExpressionAtlas
Project description:Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. Recently, dynamic epigenomic regulation, including chromatin remodeling and histone modifications by transcriptional coregulator complexes, has been shown to be involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell-type and developing stage-specific activity is largely unknown. In this study, we aimed to isolate the histone demethylase LSD1 complex from neural cells by biochemical purification. In so doing, we identified MyT1 as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed several genes, including PTEN, that were directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation. Neuro2a cells were treated with either siControl, siLSD1 or siMyT1 for 48 h (n=3)
2014-05-20 | E-GEOD-49685 | biostudies-arrayexpress
Project description:Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. Recently, dynamic epigenomic regulation, including chromatin remodeling and histone modifications by transcriptional coregulator complexes, has been shown to be involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell-type and developing stage-specific activity is largely unknown. In this study, we aimed to isolate the histone demethylase LSD1 complex from neural cells by biochemical purification. In so doing, we identified MyT1 as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed several genes, including PTEN, that were directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation.
2014-05-20 | GSE49685 | GEO
Project description:Here we performed a ChIP-seq experiment on a sample of adherent cultures of mouse neural stem cells (NS5 cell line) expressing an inducible HA-tagged version of the proneural factor MyT1 (MyT1-HA, under TetON control) after activation by doxycycline hyclate (DOX). This resulted in the generation of a genome-wide map of MyT1-HA binding to chromatin.
2016-09-09 | E-MTAB-4330 | biostudies-arrayexpress
Project description:Here we performed a microarray experiment on samples of adherent cultures of mouse neural stem cells (NS5 cell line) expressing an inducible version of the transcription factor MyT1 (MyT1-V5 TetON) under normal growth conditions and after 4 hours of treatment by doxycyline. This resulted in the generation of a genome-wide mRNA expression pattern and quantification for these cells in the two conditions.
2016-09-09 | E-MTAB-4335 | biostudies-arrayexpress
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
Project description:During brain development, histone-modifying enzymes play an important role by orchestrating transcriptional programs that regulate neuronal maturation. Lysine-Specific Demethylase 1 (LSD1, also named as KDM1A) functions as a transcriptional repressor by removing methyl groups at lysine 4 of histone H3 (H3K4). In neurons, alternative splicing can include an additional exon (exon E8a) within LSD1 transcripts, generating a LSD1+8a neuro-specific isoform. We here report that LSD1+8a isoform does not have the intrinsic ability to demethylate H3K4. LSD1+8a functions as a co-activator on its target genes by removing H3K9 repressive histone marks. We identify the supervillin protein (SVIL) as a LSD1+8a interacting partner and demonstrate that SVIL protein regulates neuronal maturation by controlling LSD1+8a mediated H3K9 demethylation. Thus, our results show that alternative splicing provides a genius mechanism by which LSD1 isoforms can acquire a dual specificity (H3K9 vs H3K4) and therefore differentially control specific gene expression patterns during brain development. In order to find some LSD1+8a regulated genes at differentiated SH-SY5Y cell lines, we infected SH-SY5Y with control or LSD1+8a shRNA, then induced differentiation with RA and BDNF, (Retinoic acid (RA) (Sigma) was added at a final concentration of 10 μM the next day after plating. After 4 days, the cells were washed three times with PBS and incubated with 50 ng/mL of Brain Derived Neural Factor (BDNF) (Millipore) in serum-free medium for 3 days), we extracted RNA from BDNF induced SH-SY5Y cells for expression analysis.Duplicates were included for Affymetrix Human transcriptome version 2 array.
2015-06-05 | E-GEOD-63097 | biostudies-arrayexpress
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
Project description:Lysine specific demethylase 1 (LSD1), which demethylates mono- and di- methylated histone H3-Lys4 as part of a complex including CoREST and histone deacetylases (HDAC), is essential for embryonic development in the mouse beyond e6.5 days. Here, we demonstrate that LSD1 expression and therefore function, is restricted to the epiblast of the post- implantation embryo. Conditional deletion of LSD1 in mouse embryonic stem (ES) cells, in vitro counterpart of the epiblast, revealed a reduction in CoREST protein, a subsequent decrease in associated HDAC activity and a global increase in Histone H3 Lys56 acetylation. Despite this biochemical perturbation, LSD1 deleted ES cells proliferate normally and retain stem cell characteristics. Loss of LSD1 causes the aberrant expression of 588 genes, including a number of transcription factors with roles in tissue development such as brachyury, Hoxb7, Hoxd8 and RARγ. Brachyury, a key-regulator of mesodermal differentiation, is a direct target gene of LSD1 and is over-expressed in e6.5 day Lsd1 genetrap embryos. Thus, LSD1 is required for the appropriate expression of key developmental regulators, via the stabilization of the LSD1/CoREST/HDAC complex, during early embryonic development. RNA samples from Lsd1Lox/Δ3 and Lsd1Δ3/Δ3 cells were compared, three biological replicates were performed.
2010-12-06 | E-GEOD-21131 | biostudies-arrayexpress
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 | GSE172370 | GEO