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The effect on gene expression of Smchd1 deletion in end stage lymphomas

ABSTRACT: Smchd1 appears to act as a tumour suppressor in the Eµ-Myc B cell lymphoma model. We find gene expression differences are most pronounced in the premalignant cells, and observe more variability in end stage lymphomas. We always detect a small number of clustered genes and imprinted genes as differentially expressed, along with others involved in tumorigenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE40880 | GEO | 2012/09/30

SECONDARY ACCESSION(S): PRJNA175423

REPOSITORIES: GEO

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The effect on gene expression of Smchd1 deletion in end stage lymphomas

Project description:Smchd1 appears to act as a tumour suppressor in the Eµ-Myc B cell lymphoma model. We find gene expression differences are most pronounced in the premalignant cells, and observe more variability in end stage lymphomas. We always detect a small number of clustered genes and imprinted genes as differentially expressed, along with others involved in tumorigenesis. The microarrays compared Smchd1 null and Smchd1 wildtype samples from end stage lymphomas. All lymphomas are on the C57BL/6 background and carry the Eµ-Myc transgene, and Smchd1 null samples are additionally homozygous for a Smchd1 genetrap allele.

2012-09-30 | E-GEOD-40880 | biostudies-arrayexpress

The effect on gene expression of Smchd1 deletion in premalignant pre-B cells

Project description:Smchd1 appears to act as a tumour suppressor in the Eµ-Myc B cell lymphoma model. We find gene expression differences are most pronounced in premalignant cells. We always detect a small number of clustered genes and imprinted genes as differentially expressed, along with others involved in tumorigenesis. The microarrays compared Smchd1 null and Smchd1 wildtype samples from premalignant pre-B cells. All samples are on the C57BL/6 background, and carry the Eµ-Myc transgene. Smchd1 null samples are additionally homozygous for a Smchd1 genetrap allele.

2012-09-30 | E-GEOD-40881 | biostudies-arrayexpress

The effect on gene expression of Smchd1 deletion in premalignant pre-B cells

2012-09-30 | GSE40881 | GEO

The effect on gene expression of Smchd1 deletion in various cell types

Project description:This SuperSeries is composed of the following subset Series: GSE40734: The effect on gene expression of Smchd1 deletion in primary MEFs, transformed MEFs and MEF tumours GSE40879: The effect on gene expression of Smchd1 deletion in pre-B cells from E17.5 Eµ-Myc embryos GSE40880: The effect on gene expression of Smchd1 deletion in end stage lymphomas GSE40881: The effect on gene expression of Smchd1 deletion in premalignant pre-B cells Refer to the individual subSeries. NOTE: all the cell types need to be analyzed separately.

2012-09-30 | E-GEOD-40992 | biostudies-arrayexpress

The effect on gene expression of Smchd1 deletion in primary MEFs, transformed MEFs and MEF tumours

Project description:Smchd1 appears to act as a tumour suppressor in the transformed fibroblast model. We find gene expression differences are most pronounced in the transformed MEFs. We always detect a small number of clustered genes and imprinted genes as differentially expressed, along with others involved in tumorigenesis. The microarrays compared Smchd1 null and Smchd1 wildtype samples from different cell types (primary MEFs, transformed MEFs, tumours derived from transformed MEFs). Wildtype mice are FVB/N and Smchd1 null mice have the MommeD1 point mutation on a FBV/N background.

2012-09-30 | E-GEOD-40734 | biostudies-arrayexpress

The effect on gene expression of Smchd1 deletion in primary MEFs, transformed MEFs and MEF tumours

2012-09-30 | GSE40734 | GEO

The effect on gene expression of Smchd1 deletion in pre-B cells from E17.5 Eµ-Myc embryos

Project description:Smchd1 appears to act as a tumour suppressor in the Eµ-Myc mouse B cell lymphoma model. We find a small number of gene expression differences at E17.5 in the pre-B cells, before phenotypic differences are observed. The microarrays compared Smchd1 null and Smchd1 wildtype E17.5 preB cell samples. All samples are on the C57BL/6 background and carry the Eµ-Myc transgene, and the Smchd1 null samples are additionally homozygous for a Smchd1 genetrap allele.

2012-09-30 | E-GEOD-40879 | biostudies-arrayexpress

A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression.

Project description:Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) is a chromatin repressor, which is mutated in >95% of Facioscapulohumeral dystrophy (FSHD) type 2 cases. In FSHD2, SMCHD1 mutations ultimately result in the presence of the cleavage stage transcription factor DUX4 in muscle cells due to a failure in epigenetic repression of the D4Z4 macrosatellite repeat on chromosome 4q, which contains the DUX4 locus. While binding of SMCHD1 to D4Z4 and its necessity to maintain a repressive D4Z4 chromatin structure are well documented, it is unclear how SMCHD1 is recruited to D4Z4, and how it exerts its repressive properties on the chromatin. Here, we employ a quantitative proteomics approach to identify and characterize novel SMCHD1 interacting proteins, and assess their functionality in D4Z4 repression. We identify 47 robust SMCHD1 interactors, of which 19 are present in D4Z4 chromatin. We demonstrate that one of these SMCHD1 interacting proteins in D4Z4, RuvB-like 1 (RUVBL1) is indeed required for maintaining DUX4 silencing in FSHD myocytes. We also confirm the interaction of SMCHD1 with EZH inhibitory protein (EZHIP), which prevents global H3K27me3 deposition by the Polycomb repressive complex PRC2, providing novel insights into the potential function of SMCHD1 in the repression of DUX4 in the early stages of embryogenesis. The SMCHD1 interactome outlined herein can thus provide further direction into research on the potential function of SMCHD1 at genomic loci where SMCHD1 is known to act, such as D4Z4 repeats, the inactive X chromosome, autosomal gene clusters, imprinted loci and telomeres.

2021-12-15 | PXD023993 | Pride

ATAC-seq in Smchd1 wild-type and Smchd1 deleted neural stem cells.

Project description:We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loc. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping.

2018-06-30 | GSE111721 | GEO

RNA-seq in Smchd1 wild-type and Smchd1 deleted differentiating male ES cells.

Project description:We sought to examine whether the non-canonical SMC protein Smchd1 plays a role in chromosome conformation. We used in situ Hi-C to analyse chromosome conformation changes upon deletion of the epigenetic regulator Smchd1 in female neural stem cells. In parallel, we analysed nucleosome accessibility using ATAC-seq, gene expression using RNA-seq, chromatin marks H3K27me3 and H3K27ac and Ctcf binding using ChIP-seq. We additionally analysed Smchd1 binding genome-wide using ChIP-seq. Together, we find that deletion of Smchd1 alters chromosome conformation at Smchd1 target genes including the inactive X chromosome, Hox genes and imprinted loci. Smchd1 deletion in differentiating ES cells results in failed Hox gene silencing. Smchd1 deletion results in gain in Ctcf binding and activation of enhancers. We propose Smchd1 functions by limiting Ctcf-mediated chromosome looping.

2018-06-30 | GSE111724 | GEO

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