Next Generation Sequencing and differential expression analysis in stem-like vs. non-stem breast cancer cells in response to HDAC1 and HDAC7 knockdown
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ABSTRACT:
PROVIDER: PRJNA544243 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9108520_1.fastq.gz | Fastqsanger.gz | |||
| SRR9108520_2.fastq.gz | Fastqsanger.gz | |||
| SRR9108530_1.fastq.gz | Fastqsanger.gz | |||
| SRR9108530_2.fastq.gz | Fastqsanger.gz | |||
| SRR9108540_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: We performed RNA-seq differential expression analysis after 72h HDAC1 and HDAC7 knockdown in order to evaluate the transcriptional regulation exerted by HDAC1 and HDAC7 in a stem-like (BPLER) vs. non-stem (HMLER) breast cancer (BrCa) cell model (please search for keywords "BPLER" or "HMLER" in GEO to access over 240 associated data sets). Results: HDAC7 knockdown by a pool of siRNAs resulted in altered expression of nearly three times the genes in BPLER vs. HMLER cells (2545 vs. 763), with the two cell types sharing altered expression of 328 genes. In stem-like BPLER cells, HDAC7 knockdown caused significant alterations in gene expression (1068 down and 1477 up). Fewer genes, less than half of BPLER, were altered in non-stem HMLER cells (448 down and 315 up), with 199 repressed and 129 activated genes shared between the two cell types. In contrast, 72h HDAC1 knockdown resulted in nearly equal numbers of altered genes in BPLER vs. HMLER cells (3187 vs. 2627), with the two cell types sharing altered expression of 637 genes. Moreover, the number of repressed (1570 vs. 1307) and activated (1617 vs. 1320) gene transcripts was similar in the two cell types In HMLER cells, HDAC7 knockdown resulted in alterations of significantly fewer gene transcripts compared to HDAC1 knockdown (508 vs. 2681), in both repressed (305 vs. 1362) and activated (203 vs. 1319) transcripts. Conclusions: Cumulatively, these results highlight that HDAC7 regulates nearly three times as many genes in stem-like compared to non-stem BrCa cells. In contrast, HDAC1 regulates equal number of genes in the same cell context, suggesting a predominant association of HDAC7 with the cancer stem cell phenotype.
2020-02-24 | GSE131631 | GEO
Project description:We sought to investigate the effects of HDAC1 and HDAC7 inhibition on genome-wide histone 3 lysine 27 acetylation (H3K27ac) in BPLER cells, a stem-like breast cancer (BrCa) cell model (please search for keyword "BPLER" in GEO to access over 30 associated datasets). Treatment of BPLER cells with MS-275 (Entinostat), a HDAC1 and HDAC3 specific inhibitor, specifically downregulates HDAC7 mRNA and protein. We carried out ChIP-seq analysis in BPLER cells treated with MS-275 and found that HDAC1/3/7 inhibition is associated with a decrease in H3K27ac at transcription start sites (TSS) and super-enhancers (SE) in stem-like BrCa cells. Importantly, these changes in chromatin landscape reduced H3K27ac at many SE-associated oncogenes, including c-MYC, CD44, CDKN1B, SLUG, VDR, SMAD3, VEGFA and XBP1. Our findings suggest that inactivation of HDAC1/3-HDAC7 axis may inhibit SE-associated oncogene expression in cancer stem cells, which can be a promising pathway to target for developing novel BrCa therapies.
2020-02-24 | GSE131436 | GEO
Project description:We analyzed the genome wide distributions of HDAC1, HDAC4, HDAC7 in Th17 cells. We find that majority of HDAC4 and HDAC7 binding sites are HDAC1 bound. TMP269 inhibits HDAC4 and HDAC7 at promoter sites of Th17 negative regulator genes, leading to their upregulation through increased H3, H4 acetylation.
2018-12-16 | GSE92531 | GEO
Project description:Title of Publication: Histone Deacetylase 7 Regulates Cell Survival and TCR Signaling in CD4/CD8 Double-Positive Thymocytes Abstract of publicaton: CD4/CD8 double-positive (DP) thymocytes express the transcriptional repressor Histone Deacetylase 7 (HDAC7), a class IIa HDAC that is exported from the cell nucleus after T cell receptor (TCR) engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in thymocytes, and regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR J segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAP kinase activity that contributes to the observed loss of viability. Remarkably, the activity of Protein Kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining auto-excitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions. Goal of Microarray experiment: We did these experiments to determine how alteration of the function of HDAC7, a site-specific and signal-dependent repressor of transcription, changes gene expression in CD4/CD8 DP thymocytes. Three biological replicate samples were prepared for each non-wild type mouse strain (Samples 7-18). Six biological replicates were prepared for the wild type strain (Samples 1-6). Total RNA was prepared from isolated CD4/CD8 Double-positive thymocytes and labeled with the Affymetrix Whole-Transcript labeling protocol. Labeled probes were hybridized to one Affymetrix Mouse Gene 1.0ST array each. Data from .cel files were normalized using RMA, in normalization groups representing each of the binary comparisons made. These binary comparisons between sample groups represent gene expression changes due to loss of HDAC7 (samples 1-3 vs. 7-9), transgenic expression of an HDAC7-VP16 fusion protein (samples 4-6 vs. 10-12), positive thymic selection (samples 1-6 vs. samples 11-15), and negative thymic selection (Samples 11-15 vs. samples 16-18).
2011-04-06 | E-GEOD-26488 | biostudies-arrayexpress
Project description:Abstract of publicaton: CD4/CD8 double-positive (DP) thymocytes express the transcriptional repressor Histone Deacetylase 7 (HDAC7), a class IIa HDAC that is exported from the cell nucleus after T cell receptor (TCR) engagement. Through signal-dependent nuclear export, class IIa HDACs such as HDAC7 mediate signal-dependent changes in gene expression that are important to developmental fate decisions in multiple tissues. We report that HDAC7 is exported from the cell nucleus during positive selection in thymocytes, and regulates genes mediating the coupling between TCR engagement and downstream events that determine cell survival. Thymocytes lacking HDAC7 are inefficiently positively selected due to a severely shortened lifespan and exhibit a truncated repertoire of TCR Jalpha segments. The expression of multiple important mediators and modulators of the response to TCR engagement is altered in HDAC7-deficient thymocytes, resulting in increased tonic MAP kinase activity that contributes to the observed loss of viability. Remarkably, the activity of Protein Kinase D, the kinase that mediates nuclear export of HDAC7 in response to TCR signaling, is also increased in HDAC7-deficient thymocytes, suggesting that HDAC7 nuclear export governs a self-sustaining auto-excitatory loop. These experiments add to the understanding of the life/death decision in thymic T cell development, define a novel function for class IIa HDACs, and point to a novel feed-forward mechanism whereby these molecules regulate their own state and mediate stable developmental transitions. Title of manuscript: Nuclear Export of Histone Deacetylase 7 During Thymic Selection Mediates Immune Self-tolerance. abstract of manuscript: Histone Deacetylase 7 (HDAC7) is a TCR signal-dependent regulator of differentiation that is highly expressed in CD4/CD8 double-positive (DP) thymocytes. Here we examine the effect of blocking TCR-dependent nuclear export of HDAC7 during thymic selection, through expression of a signal-resistant mutant of HDAC7 (HDAC7-?P) in thymocytes. We find that HDAC7-?P Transgenic thymocytes exhibit a profound block in negative thymic selection, but can still undergo positive selection, resulting in the escape of autoreactive T cells into the periphery. Gene expression profiling reveals a comprehensive suppression of the negative selection-associated gene expression program in DP thymocytes, associated with a defect in the activation of MAP kinase pathways by TCR signals. The consequence of this block in vivo is a lethal autoimmune syndrome involving the exocrine pancreas and other abdominal organs. These experiments establish a novel molecular model of autoimmunity and cast new light on the relationship between thymic selection and immune self-tolerance. Goal of Microarray experiment: We did these experiments to determine how alteration of the function of HDAC7, a site-specific and signal-dependent repressor of transcription, changes gene expression in CD4/CD8 DP thymocytes.
2011-04-06 | GSE26488 | GEO
Project description:Dynamic changes in histone acetylation patterns are mediated by the activity of histone acetyltransfereases (HATs) and histone deacetylases (HDACs) and are key events in the epigenetic regulation of gene expression. The application of HDAC inhibitors revealed a variety of T cell functions controlled by reversible lysine acetylation and HDAC1, HDAC2, HDAC3, HDAC7 and HDAC9 have been implicated in regulating T cell development and function. Nevertheless, unique functions of individual HDAC members in T cells and specific T cell functions that are regulated by HDACs are still only poorly understood. We previously showed that T cell-specific loss of HDAC1 (using the Cd4Cre deleter strain) leads to enhanced allergic airway inflammation and increased Th2 cytokine production. Interestingly, late T cell development was not impaired in these mice. However, HDAC2 was up-regulated in the absence of HDAC1, thus we hypothesized compensatory pathways/function between these two closely related class I HDAC family members in T cells. To investigate redundant and non-redundant functions of HDAC1 and HDAC2, we generated mice with a conditional T cell-specific (using Cd4Cre) combined loss of HDAC1 and HDAC2. As part of our study, we determined and compared the transcriptome of peripheral wild-type and HDAC1/2-null CD4+ T cells. Since loss of HDAC1/HDAC2 during late T cell development led to the appearance of MHC class II-selected CD4+ helper T cells that expressed CD8 lineage genes such as Cd8a and Cd8b1, we also analyzed the transcriptome of HDAC1/2-null CD4+CD8+ T cells.
2014-03-30 | E-MTAB-2184 | biostudies-arrayexpress
Project description:Histone deacetylase 1 (HDAC1) is an enzyme that promotes deacetylation of acetylated lysine residues in histones and other proteins. Histone acetylation is often associated with gene activation and expression. Los of HDAC1 leads to severe problems in development and proliferation. Moreover, it seems to be the major histone deacetylase in mouse embryonic stem cells. We used microarrays to identify putative HDAC1 target genes. Experiment Overall Design: Wild type and HDAC1 mouse embryonic stem cell, originating from same litter, were used for RNA extraction and hybridization on Affymetrix microarrays.
2007-11-13 | E-GEOD-5583 | biostudies-arrayexpress
Project description:Transcriptional profiling of hdac1 morphant zebrafish embryos in comparison to standard control injected embryos. Embryos where injected at the one cell stage with either a translation blocking morpholino (Hdac1 ATG), splice blocking morpholino (Hdac1 Splice) or Hdac1 mismatch control morpholino (Hdac1 control). RNA was extracted and compared in a two-colour hybridisation to the comman reference Standard control morpholino injected embryos. Common reference experiment, hdac1 morphants vs. standard control morphants. Biological replicates: 2 (except Splice which was technical rather than biological)
2011-01-21 | E-GEOD-26708 | biostudies-arrayexpress
Project description:Hdac1 mutant larvae comparing control WT larvae. Goal was to determine the effects of Hdac1 mutation on global larval gene expression.
2023-01-30 | GSE41640 | GEO
Project description:Overexpression HDAC7 can enhance iPS efficiency in SKO by supressing MEF2 factors We used microarrays to identify changes induced by overexpression of HDAC7 or MEF2C. MEFs were transduced with SKO plus HDAC7 or MEF2C compared to SKO plus empty vector(Flag), GFP as controls. TRIZOL cell lysates were prepared from D6 and D10.
2011-08-17 | E-GEOD-23692 | biostudies-arrayexpress