Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-44907
PROVIDER: PRJNA192521 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The aim of the experiment is to investigate whether megakaryoblastic leukemia factor-1 (MKL1) induces tenascin-C in normal mammary epithelial HC11 and tumor mammary epithelial 4T1 cell lines, as well as to identify other genes that are transcriptionally regulated by MKL1. For this purpose, we compared the transcriptomes of HC11 and 4T1 cell lines stably expressing the full length (FL) MKL1 protein (HC11-FL and 4T1-FL cell lines) to respective control cell lines stably transfected with an empty vector (HC11-control and 4T1-control cell lines).
2011-06-10 | E-MEXP-3232 | biostudies-arrayexpress
Project description:We have previously shown that HC11 mammary epithelial cells react strongly to the overexpression of megakaryoblastic leukemia-1 (Mkl1) with induction of tenascin-C expression. The present study was designed to find genes co-regulated with tenascin-C by Mkl1 in a SAP domain-dependent manner and without the involvement of serum response factor (SRF). For this purpose, we compared the transcriptomes of three stable HC11 cell strains that either overexpress full length Mkl1-RFP (HC11-FL), Mkl1-RFP with a mutated SRF-interaction site (HC11-mutB1) or Mkl1-RFP with a deletion of the SAP domain (HC11-ΔSAP).
2014-02-06 | GSE44907 | GEO
Project description:Transcription profiling by array of HC11 mammary epithelial cell strains stably expressing different variants of the transcriptional regulator megakaryoblastic leukemia-1 (Mkl1)
2015-01-17 | E-GEOD-44907 | ExpressionAtlas
Project description:We have previously shown that HC11 mammary epithelial cells react strongly to the overexpression of megakaryoblastic leukemia-1 (Mkl1) with induction of tenascin-C expression. The present study was designed to find genes co-regulated with tenascin-C by Mkl1 in a SAP domain-dependent manner and without the involvement of serum response factor (SRF). For this purpose, we compared the transcriptomes of three stable HC11 cell strains that either overexpress full length Mkl1-RFP (HC11-FL), Mkl1-RFP with a mutated SRF-interaction site (HC11-mutB1) or Mkl1-RFP with a deletion of the SAP domain (HC11-ΔSAP). HC11 cell strains stably expressing either FL-, mutB1- or ∆SAP-Mkl1-RFP clones were grown in triplicates in 0.03% FCS/RPMI medium without EGF for 48 h before total RNA was extracted. RNA was converted into labeled cDNA and hybridized to Affymetrix GeneChip Mouse Gene 1.0 ST arrays. RMA normalized expression values were calculated with the affy package from the Bioconductor 2.4 release (1) and differentially expressed genes were identified using moderated t-statistics calculated with the empirical Bayes method as implemented in the Bioconductor limma package (2). To be considered as differentially expressed between HC11-mutB1 and HC11-FL as well as HC11-∆SAP and HC11-FL cell lines, genes had to pass the filters: adjusted P-value ≤ 0.01 (with Benjamin-Hochberg false discovery correction), a minimum absolute linear fold change difference of 2.0 and a minimum average expression value of 4.0 (log2). References: (1) Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., Hornik, K., Hothorn, T., Huber, W., Iacus, S., Irizarry, R., Leisch, F., Li, C., Maechler, M., Rossini, A., Sawitzki, G., Smith, C., Smyth, G., Tierney, L., Yang, J., Zhang, J. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biology 5, R80 (2) Smyth, G. K., Speed, T. (2003) Normalization of cDNA microarray data. Methods 31, 265-273
2014-02-06 | E-GEOD-44907 | biostudies-arrayexpress
Project description:Megakaryoblastic Leukemia 1 and 2 (MKL1 and 2) are coactivators of the transcription factor Serum Response Factor (SRF). We recently showed that depletion of MKL1 and 2 abolished HCC xenograft growth, associated with oncogene-induced senescence. To identify suitable MKL target genes mediating these effects, we performed microarray analyses using HuH7 hepatocellular carcinoma cells stably expressing shRNA against MKL1/2 (HuH7 MKL1/2 KD). We therefore used a Affymetrix oligonucleotide array and filtered for genes whose expression in HuH7 MKL1/2 KD cells was reduced by a factor of at least 2.5 as compared to control HuH7 cells.
2017-01-01 | GSE88974 | GEO
Project description:Megakaryoblastic Leukemia 1 (MKL1) was identified as part of the t(1;22) translocation specific to acute megakaryoblastic leukemia, but nothing is known regarding its role in hematopoiesis. Here we show that overexpression of MKL1 enhances megakaryocytic differentiation of the Human Erythroleukemia cell line (HEL). Microarray analysis reveals that MKL1 promotes expression of megakaryocyte-specific genes such as glycoprotein V (GP5), as well as cytoskeletal and adhesion molecule genes relevant to megakaryocyte differentiation and proplatelet formation. MKL1 is a transcriptional coactivator of Serum Response Factor. In this study, MKL1 also upregulates known SRF targets. Results provide insight into the role of MKL1 in megakaryocytopoiesis.
2008-12-10 | GSE13710 | GEO
Project description:We identified two isoforms of human MKL1 that differ in their N-terminal domains. Since MKL1 is a transcriptional coactivator of SRF and regulates many SRF target genes, we wanted to analyze if transcription is differentially regulated by the two isoforms upon stimulation of the Rho-actin-MKL1-SRF pathway. Activity of the Rho-actin-MKL1 pathway was induced in EcR293 cell lines stably over-expressing the empty vector control, a 5’UTR-full length MKL1_S construct, or a 5’UTR-full length MKL1_L construct by LPA treatment.
2015-05-14 | E-GEOD-47209 | biostudies-arrayexpress
Project description:Megakaryoblastic leukemia 1 (MKL1) promotes the regulation of essential cell processes, including actin cytoskeletal dynamics by co-activating serum response factor. Recently, the first human case with MKL1 deficiency, leading to a novel primary immunodeficiency, was identified. We report a second family with two siblings with a homozygous frameshift mutation in MKL1. The index case deceased as an infant from progressive and severe pneumonia by Pseudomonas aeruginosa and poor wound healing. The younger sib was preemptively transplanted shortly after birth. The immunodeficiency was marked by a pronounced actin polymerization defect and a strongly reduced motility and chemotactic response by MKL1-deficient neutrophils. Apart from the lack of MKL1, subsequent proteomic and transcriptomic analyses of patient neutrophils revealed actin and several actin-related proteins to be downregulated, confirming a role for MKL1 as transcriptional co-regulator. Degranulation was enhanced upon suboptimal neutrophil activation, while production of reactive oxygen species was normal. Neutrophil adhesion was intact but without proper spreading. The latter could explain the observed failure in firm adherence and transendothelial migration under flow conditions. No apparent defect in phagocytosis and bacterial killing was found. Also monocyte-derived macrophages showed intact phagocytosis; lymphocyte counts and proliferative capacity were normal. Non-hematopoietic primary patient fibroblasts demonstrated defective differentiation into myofibroblasts but normal migration and filamentous actin (F-actin) content, most probably due to compensatory mechanisms of MKL2, which is not expressed in neutrophils. Our findings extend current insight into the severe immune dysfunction in MKL1 deficiency, with cytoskeletal dysfunction and defective extravasation of neutrophils as most prominent features.
2020-03-16 | GSE134644 | GEO
Project description:HEK293 stably expressing Autoimmune regulator protein
| PRJNA117587 | ENA
Project description:Estrogen receptor (ERα) is central in driving the development of hormone-dependent breast cancers. A major challenge in treating these cancers is to understand and struggle endocrine resistance. We have previously shown that the Megakaryoblastic Leukemia 1 (MKL1) protein, a master regulator of actin dynamic and cellular motile functions, directs down-regulation of ERα and hormonal escape of estrogen-responsive breast cancer cell lines. In the present study, we decipher the underlining mechanisms by tracking functional changes in ERα activity. We demonstrate through gene expression microarray analysis that the constitutive activation of MKL1 in ERα-positive MCF7 breast cancer cells induces a transition from a luminal to a basal-like phenotype and suppresses almost all regulations of gene expression by estrogen. Chromatin immunoprecipitation of DNA coupled to high-throughput sequencing (ChIP-Seq) shows a profound reprogramming in ERα cistrome associated with a massive loss of ERα binding sites (ERBSs) generally associated with lower ERα-binding activity. Novel ERBSs appear to be associated with EGF and RAS signaling pathways. ERα dynamic was further impacted by a displacement of its monomer/dimer equilibrium towards its monomer state, associated with a redistribution of the normally nuclear ERα protein to the entire cell volume. We next show that the combination of these remodeled dynamics of ERα alters its interactions with genomic and non-genomic partners. In particular, the formation of ERα/kinase complexes was promoted by the constitutive activation of MKL1. Hence, MKL1-induced transition of ER-positive breast cancer cells from luminal to basal-like phenotype shifts ERα activities from genomic to non-genomic function.
2019-12-31 | GSE107476 | GEO