Effects of Lrf (encoded by Zbtb7a) deletion on gene expression in mouse embryonic fibroblast (MEF)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE70680 | GEO | 2015/07/10
SECONDARY ACCESSION(S): PRJNA289350
REPOSITORIES: GEO
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Project description:LRF is reported as a transcription repressor, but its transcription target genes are not completely known We compared the gene expression difference between control and Lrf deleted MEF by microarray Lrfflox/flox MEFs were transduced with MSCV-PIG-Cre or empty control vector retroviruses for 2 days at passage 2. After selection with puromycin for 2 days, total RNAs were purified using the RNAeasy Mini Kit (Qiagen) and treated with RNase-free DNase set (Qiagen). RNAs from two independent experiments were labelled and hybridized using Affymetrix GeneChip® HT Mouse Genome 430 arrays by the Beth Israel Deaconess Medical Center Genomics and Proteomics
2015-07-10 | E-GEOD-70680 | biostudies-arrayexpress
Project description:Hemoglobinopathies, including sickle cell disease and _-thalassemia, are global public health concerns. Induction of fetal-type hemoglobin (HbF) is a promising means to treat these disorders; however, precisely how HbF expression is silenced in adult erythroid cells is not fully understood. Here, we show that the LRF/ZBTB7A transcription factor is a potent repressor of HbF production. LRF inactivation derepresses embryonic/fetal _-globin expression in mouse and human adult erythroid cells. We employed genome-wide analysis of the transcriptome, chromatin accessibility and LRF occupancy sites, and demonstrate that LRF occupies the _-globin loci and maintains nucleosome density necessary for _-globin silencing. LRF confers its repressive activity through a unique NuRD repressor complex independent of BCL11A. Strikingly, human erythroid lines lacking both LRF and BCL11A exhibited almost a complete switch in expression from adult- to fetal-type globin, suggesting that these two factors cumulatively represent the near entirety of _-globin repressive activity in adult erythroid cells. RNA-seq, LRF ChIP-seq and ATAC-seq assays were used to investigtae LRF binding, effect of LRF depletion on transcription and chromatin landscape in mouse and human cells.
2016-01-15 | E-GEOD-74977 | biostudies-arrayexpress
Project description:Hemoglobinopathies, including sickle cell disease and _-thalassemia, are global public health concerns. Induction of fetal-type hemoglobin (HbF) is a promising means to treat these disorders; however, precisely how HbF expression is silenced in adult erythroid cells is not fully understood. Here, we show that the LRF/ZBTB7A transcription factor is a potent repressor of HbF production. LRF inactivation derepresses embryonic/fetal _-globin expression in mouse and human adult erythroid cells. We employed genome-wide analysis of the transcriptome, chromatin accessibility and LRF occupancy sites, and demonstrate that LRF occupies the _-globin loci and maintains nucleosome density necessary for _-globin silencing. LRF confers its repressive activity through a unique NuRD repressor complex independent of BCL11A. Strikingly, human erythroid lines lacking both LRF and BCL11A exhibited almost a complete switch in expression from adult- to fetal-type globin, suggesting that these two factors cumulatively represent the near entirety of _-globin repressive activity in adult erythroid cells.
2016-01-15 | GSE74977 | GEO
Project description:We used microarrays to analyze the global gene expression and identified differentially expressed gene list between wild-type anterior prostates and Pb-Cre4;PtenLoxP/LoxP anterior prostates, Pb-Cre4;PtenLoxP/LoxP;LrfLoxP/LoxP anterior prostates at 12 weeks of age. Prostate-specific Pten deletion (Pb-Cre4;PtenLoxP/LoxP) results in prostate intraepithelial neoplasia (PIN) which, following a long latency, can progress to high-grade adenocarcinoma, albeit with minimally invasive and metastatic features. However, inactivation of Lrf in the prostate epithelium in combination of Pten results in aggressive prostate tumors. To understand the molecular mechanisms by which loss of Lrf promotes Pten-loss-driven prostate tumorigenesis, we conducted transcriptome comparison of three wild-type anterior prostates, three Pb-Cre4;PtenLoxP/LoxP PIN, and three Pb-Cre4;PtenLoxP/LoxP;LrfLoxP/LoxP anterior prostate tumors.
2013-05-19 | E-GEOD-46473 | biostudies-arrayexpress
Project description:To examine whether LRF protein could bind cis-regulatory elements in the genes that LRF regulates. We performed Chromatin immunoprecipitation followed by deep-sequencing (ChIPseq) on activated T cells using an in vivo biotinylation and streptavidin pull-down approach.
2022-03-30 | GSE149993 | GEO
Project description:B cells are indispensable for humoral immunity, as they ultimately give rise to antibody-secreting plasma cells. During T cell-dependent antibody responses, naive B cells form germinal centers (GCs), a distinct histologic structure found in secondary lymphoid organs. Naive B cells become activated upon interaction with T cells and antigen presenting cells, and begin to rapidly proliferate and form the characteristic GC structure. To elucidate the overall effect of LRF loss in the GCB cell transcriptome, gene expression microarray analysis of FACS-sorted GCB cells was performed. LRF Flox/+ mb-1 Cre+ mice were used as a control to normalize the potential effects of Cre recombinase, and four RNA samples for each genotype were used for the analysis. B cell-specific LRF knockout (LRF Flox/Flox mb-1 Cre+) and control (LRF Flox/+ mb-1 Cre+) mice (4 each) were immunized with sheep red blood cells, and GCB cells were FACS-sorted 7 days later.
2011-04-08 | E-GEOD-28449 | biostudies-arrayexpress
Project description:LRF, which is encoded by the ZBTB7A gene and formerly known as POKEMON (POK erythroid myeloid ontogenic factor), was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue interacting with BCL6 (B-cell lymphoma 6). LRF is a transcription factor that is broadly expressed in hematopoietic lineage cells, but its expression is particularly high in erythroblasts and germinal center (GC) B-cells. The goal of this study is to assess the effect of LRF loss on the LT-HSC transcriptome. Nine days after injection of adult mice with polyinosinic polycytidylic acid (pIpc) to activate Cre, total RNAs were isolated from double-sorted LT-HSCs from LRF Flox/+ Mx1-Cre+ and LRF Flox/Flox Mx1-Cre+ mice and processed for microarray analysis. We performed gene expression microarray analysis of FACS-sorted LT-HSCs (LSK IL7Ra-Flt3-CD150+CD48-) to assess the effect of Lrf loss on the LT-HSC transcriptome. Zbtb7a Flox/+ Mx1-Cre+ mice were used as a control to normalize the potential effects of Cre recombinase. LT-HSCs were FACS-sorted from three Lrf knockout (Zbtb7a Flox/Flox Mx1-Cre+) and two control (Zbtb7a Flox/+ Mx1-Cre+) mice, nine days after the first pIpC injection.
2012-10-26 | E-GEOD-41839 | biostudies-arrayexpress
Project description:ChIP-seq for LRF/ZBTB7A in untransfected or LRF/ZBTB7A-overexpressing K562 cells, with or without hemin/EPO treatment and in K562 LRF/ZBTB7A-Knockdown cells
2022-07-13 | GSE200135 | GEO
Project description:LRF, which is encoded by the ZBTB7A gene and formerly known as POKEMON (POK erythroid myeloid ontogenic factor), was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue interacting with BCL6 (B-cell lymphoma 6). LRF is a transcription factor that is broadly expressed in hematopoietic lineage cells, but its expression is particularly high in erythroblasts and germinal center (GC) B-cells. The goal of this study is to assess the effect of LRF loss on the LT-HSC transcriptome. Nine days after injection of adult mice with polyinosinic polycytidylic acid (pIpc) to activate Cre, total RNAs were isolated from double-sorted LT-HSCs from LRF Flox/+ Mx1-Cre+ and LRF Flox/Flox Mx1-Cre+ mice and processed for microarray analysis.
2012-10-26 | GSE41839 | GEO
Project description:To examine how the cluster composition of IELp and their transcriptomic signatures were affected by LRF disruption, single-cell gene expression of IELp from control (Cd4 Cre–Lrffl/fl) and LRF KO(Cd4 Cre+Lrffl/fl )mice were determined by scRNAseq
2022-03-30 | GSE149985 | GEO