MBD2 and H3K4Me3 CUT&RUN-sequencing in C2C12 cells undergoing myogenic differentiation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE183520 | GEO | 2021/09/08
REPOSITORIES: GEO
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Project description:MBD2 and H3K4Me3 CUT&RUN-sequencing in C2C12 cells undergoing myogenic differentiation
| PRJNA761114 | ENA
Project description:We show that in vivo MBD2 is mainly recruited to CpG island promoters that are highly methylated. We also report that MBD2 binds to a subset of CpG island promoters that are characterized by the presence of active histone marks and RNA polymerase II (Pol2). At such sites, MBD2 binds downstream of the transcription start site. Active promoters bound by MBD2 show low to medium gene expression levels and H3K36me3 deposition suggesting a putative role for MBD2 in blocking polymerase II (Pol2) elongation at these promoters.
2014-07-03 | GSE54693 | GEO
Project description:Little is known about the roles of methyl-CpG-binding domain protein 2 (MBD2), a “reader” of DNA methylation, in T-cell acute lymphoblastic leukemia (T-ALL). Here, we investigated the role of MBD2 in T-ALL by using an Mbd2 knockout mouse model. We found that MBD2 ablation impeded the progression and maintenance of Notch1-driven T-ALL.Our data reveals essential roles for MBD2 in lymphopoiesis and T-ALL and support an intriguing potential of MBD2 as a therapeutic target for T-ALL. To explore potential mechanisms underlying the anti-ALL effects of MBD2 ablation, leukemic cells were harvested from mice transplanted with WT or Mbd2-/- T-ALL cells, and their global gene expression profiles (GEP) were compared. Double positive (DP) thymocytes were isolated and used as a normal control.
2017-10-23 | GSE105763 | GEO
Project description:We show that in vivo MBD2 is mainly recruited to CpG island promoters that are highly methylated. We also report that MBD2 binds to a subset of CpG island promoters that are characterized by the presence of active histone marks and RNA polymerase II (Pol2). At such sites, MBD2 binds downstream of the transcription start site. Active promoters bound by MBD2 show low to medium gene expression levels and H3K36me3 deposition suggesting a putative role for MBD2 in blocking polymerase II (Pol2) elongation at these promoters. To gain further insight into the function of and epigenetic regulation by MBD2 we generated a tagged version of the protein and stably expressed it in the MCF-7 cell line. We mapped genome wide binding of MBD2 by ChIP sequencing (ChIP-seq) and together with base resolution whole genome bisulfite sequencing (WGBS) we were able to determine the methylation content and the role of methylation density at MBD2 enriched regions. We further dissected MBD2 binding properties, taking advantage of a large set of ChIP-seq data including active histone marks, RNA polymerase II (POL2) and strand specific RNA-seq.
2014-07-03 | E-GEOD-54693 | biostudies-arrayexpress
Project description:Mice deficient in MBD2 (Mbd2-/-) were treated with 2% dextran sulfate sodium or normal drinking water for 6 continuous days. A single cell suspension of colon lamina propria and epithelium was isolated, with monocytes (CD11b+ Ly6CHi, MHC-II+/-), macrophages (CD11b+ Ly6C-MHC-II+), cDC2s (CD11b- CD11c+ CD103+) and epithelial cells (CD45- EpCAM+) purified by FACS. Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer and anti-helminth responses, its role in controlling colitis has yet to be defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease. In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2-/- mice displayed dramatically worse pathology than wild type controls during dextran sulphate sodium (DSS) induced colitis, with increased inflammatory (IL-1β+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis severity. Our identification of this dual role for Mbd2 in regulating the inflammatory capacity of both CD11c+ cells and ECs highlights how epigenetic control mechanisms may limit intestinal inflammatory responses.
2020-02-26 | GSE134281 | GEO
Project description:Mice deficient in MBD2 (Mbd2-/-) were treated with 2% dextran sulfate sodium or normal drinking water for 6 continuous days. A single cell suspension of colon lamina propria and epithelium was isolated, with monocytes (CD11b+ Ly6CHi, MHC-II+/-), macrophages (CD11b+ Ly6C-MHC-II+), cDC2s (CD11b- CD11c+ CD103+) and epithelial cells (CD45- EpCAM+) purified by FACS. Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer and anti-helminth responses, its role in controlling colitis has yet to be defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease. In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2-/- mice displayed dramatically worse pathology than wild type controls during dextran sulphate sodium (DSS) induced colitis, with increased inflammatory (IL-1β+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis severity. Our identification of this dual role for Mbd2 in regulating the inflammatory capacity of both CD11c+ cells and ECs highlights how epigenetic control mechanisms may limit intestinal inflammatory responses.
2020-02-26 | GSE134280 | GEO
Project description:The heterogeneous collection of NuRD complexes can be grouped into the MBD2 or MBD3 containing complexes MBD2-NuRD and MBD3-NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here we show when depleting cells for MBD2, the MBD2 bound genes increase their activity, whereas MBD2 plus MBD3 bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. This suggests a functional connection between MBD2 binding to chromatin and splicing.
2013-02-08 | GSE41003 | GEO
Project description:Methylated DNA binding protein 2 (MBD2) has been shown to bind specific methylated promoters and suppress transcription. Here we systematically investigate MBD2 suppression by overexpressing MBD2 in MCF-10A cells and generating gene expression profiles of overexpressing cells and normal MCF-10A cells.
2013-06-17 | GSE47873 | GEO
Project description:The proposed use of Foxp3+ T-regulatory (Treg) cells as potential cellular therapy in patients with autoimmune diseases, or post-hemopoietic stem cell or organ transplantation, requires a sound understanding of the transcriptional regulation of Foxp3 expression. Conserved CpG dinucleotides in the Treg-specific demethylated region (TSDR) upstream of Foxp3 are demethylated only in stable, thymic-derived Foxp3+ Tregs. Since methyl-binding domain (Mbd) proteins recruit histone-modifying and chromatin-remodeling complexes to methylated sites, we tested whether targeting of Mbd2 might promote demethylation of Foxp3 and thereby promote Treg numbers or function. Surprisingly, while ChIP analysis showed Mbd2 binding to the Foxp3-associated TSDR site in Tregs, Mbd2 targeting by homologous recombination or siRNA decreased Treg numbers and impaired Treg suppressive function in vitro and in vivo. Moreover, we found complete TSDR demethylation in WT Tregs but >75% methylation in Mbd2-/- Tregs, whereas re-introduction of Mbd2 into Mbd2-null Tregs restored TSDR demethylation, Foxp3 gene expression and Treg suppressive function. Lastly, Mbd2-/- Tregs had markedly binding of the DNA demethylase enzyme, Tet2, in the TSDR region. These data show that Mbd2 has a key role in promoting TSDR demethylation, Foxp3 expression and Treg suppressive function. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of MBD2–/– mice, compared to wild type control (all Balb/c background).
2013-09-01 | E-GEOD-48653 | biostudies-arrayexpress
Project description:The heterogeneous collection of NuRD complexes can be grouped into the MBD2 or MBD3 containing complexes MBD2-NuRD and MBD3-NuRD. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here we show a strong enrichment for MBD2 at methylated CpG sequences, whereas CpGs bound by MBD3 are devoid of methylation. Gene activity of MBD2 bound genes is four fold lower as compared to genes bound by MBD3. When depleting cells for MBD2, the MBD2 bound genes increase their activity, whereas MBD2 plus MBD3 bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. This suggests a functional connection between MBD2 binding to chromatin and splicing.
2013-02-08 | GSE41006 | GEO