Genome-wide maps of DNA cytosine methylation state in during normal differentiation commitment in hematopoietic stem cells (HSC) and in Special AT-rich sequence-binding protein1 (Satb1) - deficient HSC
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE44304 | GEO | 2013/04/07
SECONDARY ACCESSION(S): PRJNA189409
REPOSITORIES: GEO
Similar Datasets
Project description:Our data show Satb1 deficiency leads to alterations in DNA cytosine methylation and a commitment-primed epigenetic state in HSCs. Examination of DNA cytosine methylation in wild type HSC and differentiation-committed progenitors as well as in wild type HSC and HSC lacking Satb1 (n=2 each).
2013-04-07 | E-GEOD-44304 | biostudies-arrayexpress
Project description:To understand gene expression signatures between wild-type and Satb1-deficient cells To examine genes regulated by Satb1 expression, sets of microarrays were conducted with Lin- c-kitHi Sca-1+ Flt3- HSC-enriched cells, Lin- c-kitHi Sca-1+ Flt3+LMPP-enriched cells, and Lin- c-kitLo Sca-1Lo IL7Rα+ CLP-enriched cells derived from E18.5 FL of Satb1-null mice or their WT littermates.
2013-03-20 | E-GEOD-45299 | biostudies-arrayexpress
Project description:To understand gene expression signatures between wild-type and Satb1-deficient cells
2013-03-20 | GSE45299 | GEO
Project description:Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3’UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function. Gene expression profiling of freshly isolated CD4+ T cells, separated into CD25 negative and positive subpopulations, from three different donors. FOXP3 is stably and constitutively expressed at a high level in CD4+CD25+ regulatory T cells and at a low level in CD4+CD25- cells.
2011-08-13 | E-GEOD-15390 | biostudies-arrayexpress
Project description:Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3’UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function.
2011-08-14 | GSE15390 | GEO
Project description:Hematopoietic stem cells (HSCs) are now recognized as a heterogeneous population in self-renewing and differentiation capabilities. However, fundamental mechanisms governing the heterogeneity remain uncertain. We here show that special AT-rich sequence-binding protein 1 (SATB1), a global chromatin organizer, is involved in the mechanisms. Analyzing hematological lineage-restricted SATB1 knock out mice proved that SATB1 is indispensable for both self-renewal and normal differentiation of adult HSCs. Using SATB1/Tomato knock-in mice, we subdivided HSCs according to SATB1 intensity. Culture experiments and RNA-sequencing revealed essential differences between SATB1- and SATB1+ HSCs regarding lineage potential.
2018-06-14 | GSE94630 | GEO
Project description:Base excision repair is initiated by DNA glycosylases that recognize specific altered bases. DNA glycosylases for oxidized bases carry both a glycosylase activity that removes the faulty base and an apyrimidinic/apurinic lyase activity that introduces a single-strand DNA incision. In particular, the CUT domains within the CUX1 and CUX2 proteins were recently shown to interact with the 8-oxoguanine (8-oxoG) DNA glycosylase and stimulate its enzymatic activities. SATB1, which contains two CUT domains, was originally characterized as a T cell-specific genome organizer whose aberrant overexpression in breast cancer can promote tumor progression. Here we investigated the involvement of SATB1 in DNA repair. SATB1 knockdown caused a delay in DNA repair following exposure to H2O2, an increase in OGG1-sensitive oxidized bases within genomic DNA, and a decrease in 8-oxoG cleavage activity in cell extracts. In parallel, we observed an increase in phospho-CHK1 and ?-H2AX levels and a decrease in DNA synthesis. Conversely, ectopic expression of SATB1 accelerated DNA repair and reduced the levels of oxidized bases in genomic DNA. Moreover, an enhanced GFP-SATB1 fusion protein was rapidly recruited to laser microirradiation-induced DNA damage. Using purified proteins, we showed that SATB1 interacts directly with OGG1, increases its binding to 8-oxoG-containing DNA, promotes Schiff base formation, and stimulates its glycosylase and apyrimidinic/apurinic lyase enzymatic activities. Structure/function analysis demonstrated that CUT domains, but not the homeodomain, are responsible for the stimulation of OGG1. Together, these results identify another CUT domain protein that functions both as a transcription factor and an accessory factor in base excision repair.
| S-EPMC5077210 | biostudies-other
Project description:Hut78 cell line was used as Sezary syndrome cell model. Comparative transcriptome profiles of SATB1 transduced Hut78 cells (Hut78-SATB1) relative to empty MIG vector transduced control Hut78 cells (Hut78-MIG) were analyzed. The primary goal is to establish a list of genes with differential expression between SATB1 transduced Hut78 cells and control Hut78 cells to identify the gene expression regulation effect of SATB1 expression in Sezary cells. Two color experiment, 3 biological replicates (3 unique cell clones) with Hut78 cells, each compared with a distinct individual clone from cells transduced with empty MIG vector.
2011-12-01 | E-GEOD-24951 | biostudies-arrayexpress
Project description:Hut78 cell line was used as Sezary syndrome cell model. Comparative transcriptome profiles of SATB1 transduced Hut78 cells (Hut78-SATB1) relative to empty MIG vector transduced control Hut78 cells (Hut78-MIG) were analyzed. The primary goal is to establish a list of genes with differential expression between SATB1 transduced Hut78 cells and control Hut78 cells to identify the gene expression regulation effect of SATB1 expression in Sezary cells.
2011-12-01 | GSE24951 | GEO