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Loss of an oligodendrocyte specific silencer element provides a framework to assess the pathogenic impact of lamin B1 structural variants

ABSTRACT: Loss of an oligodendrocyte specific silencer element provides a framework to assess the pathogenic impact of lamin B1 structural variants

PROVIDER: PRJNA997958 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25405043_1.fastq.gz	Fastqsanger.gz
	SRR25405043_2.fastq.gz	Fastqsanger.gz
	SRR25405044_1.fastq.gz	Fastqsanger.gz
	SRR25405044_2.fastq.gz	Fastqsanger.gz
	SRR25405047_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Loss of an oligodendrocyte specific silencer element provides a framework to assess the pathogenic impact of lamin B1 structural variants

Project description:The role of non-coding regulatory elements and how they might contribute to tissue type specificity of disease phenotypes is poorly understood. Autosomal Dominant Leukodystrophy (ADLD) is a fatal, adult-onset, neurological disorder that is characterized by extensive CNS demyelination. Most cases of ADLD are caused by tandem genomic duplications involving the lamin B1 gene (LMNB1) while a small subset are caused by genomic deletions upstream of the gene. Utilizing data from recently identified families that carry LMNB1 gene duplications but that do not exhibit demyelination, ADLD patient tissues, CRISPR modified cell lines and mouse models, we have identified a novel silencer element that is lost in ADLD patients and that specifically targets overexpression only to oligodendrocytes. This element consists of CTCF binding sites that mediate three-dimensional chromatin looping involving the LMNB1 and the recruitment of the PRC2 repressor complex. Loss of the silencer element in ADLD identifies a previously unknown role for silencer elements in tissue specificity and disease causation.

2024-12-02 | GSE238093 | GEO

An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants

Project description:An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants

| PRJNA1204085 | ENA

An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants

Project description:Autosomal Dominant Leukodystrophy (ADLD) is a fatal, adult-onset neurological disorder characterized by extensive CNS demyelination. Most cases of ADLD are caused by tandem genomic duplications involving the lamin B1 gene (LMNB1), while a small subset result from genomic deletions upstream of the gene. However, recently identified families carrying the LMNB1 gene duplication, but lacking demyelination, have been found, suggesting the involvement of a non-coding regulatory element. To investigate this, a LMNB1-specific aCGH was conducted using DNA from these newly discovered families and canonical ADLD cases. This approach identified a genomic region, belonging to a silencer element, that is absent in ADLD cases with a LMNB1 duplication or deletion.

2024-12-29 | GSE285491 | GEO

An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants.

Project description:The role of non-coding regulatory elements and how they might contribute to tissue type specificity of disease phenotypes is poorly understood. Autosomal Dominant Leukodystrophy (ADLD) is a fatal, adult-onset, neurological disorder that is characterized by extensive CNS demyelination. Most cases of ADLD are caused by tandem genomic duplications involving the lamin B1 gene (LMNB1) while a small subset are caused by genomic deletions upstream of the gene. Utilizing data from recently identified families that carry LMNB1 gene duplications but do not exhibit demyelination, ADLD patient tissues, CRISPR edited cell lines and mouse models, we have identified a silencer element that is lost in ADLD patients and that specifically targets expression to oligodendrocytes. This element consists of CTCF binding sites that mediate three-dimensional chromatin looping involving LMNB1 and the recruitment of the PRC2 transcriptional repressor complex. Loss of the silencer element in ADLD identifies a role for non-coding regulatory elements in tissue specificity and disease causation.

| S-EPMC11799162 | biostudies-literature

Molecular maps of the Lamin B1-associated genomic regions in oligodendrocyte lineage cells

Project description:Molecular maps of the Lamin B1-associated genomic regions in oligodendrocyte lineage cells

| PRJNA561578 | ENA

An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development

Project description:Rag1 and Rag2 gene expression in CD4+CD8+ double positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer. However, the mechanistic basis for ASE activity is unknown. Here we show that the ASE physically interacts with the distant Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub. Moreover, we show that the ASE functions as a classical enhancer that can potently activate these promoters in the absence of the silencer or other locus elements. In thymocytes lacking the chromatin organizer SATB1, we identified a partial defect in Tcra gene rearrangement that was associated with reduced expression of Rag1 and Rag2 at the DP stage. SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters. Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes. Sequencing of Satb1-ChIP and input control from 6 wk old thymus

2015-02-25 | E-GEOD-66248 | biostudies-arrayexpress

Lamin and Lamin B receptor knockout

Project description:influence of lamin B rereceptor knockout and lamin A/C knockout on gene expression in cultured myoblast cells and in striated muscle tissue knockout samples are obtained by mating of heterozygous animals. Homozygous KO and wt animals of one litter are compared. Two boilogical replicates of KO samples are processed in parallel. wt samples are used as controls. One wt sample is processed per KO litter. Where appropriate two wt samples are used as biological replicates.

2013-01-28 | E-GEOD-37076 | biostudies-arrayexpress

Molecular maps of the Lamin B1-associated genomic regions in oligodendrocyte lineage cells

Project description:This study addresses the mechanisms regulating the identity of oligodendrocyte progenitor cells (OPC) in physiological conditions and the pathological mechanisms leading to autosomal adrenoleukodystrophy (ADLD), a disease caused by persistence of lamin B1 (LMNB1) expression in oligodendrocytes (OL). Using mouse primary OPCs and a novel technique for the study of DNA-protein interaction, we identify the genomic regions showing dynamic interactions with LMNB1. The transition from ESC to OPC revealed increased association of gene involved in pluripotency and neuronal function and decreased association of gene categories associated with the differentiation of OPC into OL (including genes regulating epigenetic modifiers, RNA processing and protein phosphorylation). Since LMNB1 declines during the transition from OPC to OL, and its persistent expression has been linked to pathological conditions, such as ADLD, we further identified the molecular maps of genome-lamina reorganization in OPC differentiating into OL which continue to express LMNB1 (mOLLMNB1). The transition from OPC to mOLLMNB1 revealed increased association to LMNB1 of genomic regions encoding for lipid metabolism and protein phosphorylation, and decreased association of genes negatively regulating differentiation. These data highlight the importance of LMNB1 in physiological conditions and identify mechanisms responsible for late onset ADLD.

2020-03-16 | GSE135834 | GEO

Quantification of mature lamin A and progerin in HGPS patient cells

Project description:The ratio of progerin to mature lamin A correlates with disease severity in HGPS patients, and can be used to assess the effectiveness of therapies aimed at lessening aberrant splicing and/or progerin farnesylation. We have developed the first non-immunological method, based on a targeted MS approach and the use of isotope-labelled internal standards, that reliably quantifies the levels of wild-type lamin A and farnesylated progerin in cells from HGPS patients.

2023-08-26 | PXD036318 | JPOST Repository

Lamin and Lamin B receptor knockout

Project description:influence of lamin B rereceptor knockout and lamin A/C knockout on gene expression in cultured myoblast cells and in striated muscle tissue

2013-01-28 | GSE37076 | GEO

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