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Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [sorted cells RNA-seq]

ABSTRACT: Smarcad1 is one of the most conserved chromatin remodelling factors, from yeast to human, with suggested functions in gene silencing, heterochromatin maintenance and genome stability. However, its role in tissue function is poorly understood. As this factor is highly expressed in the stem- and proliferative zone in the intestinal epithelium, we explored the role of this factor in this tissue. Intestine tissue-specific deletion of Smarcad1 resulted in notable changes in gene expression in the small intestine, colon and organoids from small intestine. Strikingly, we found an increase of expression of several genes linked to innate immunity and a dramatic increase of a Bglap3 coding for an osteocalcin isoform, a protein normally expressed in osteoblasts.

ORGANISM(S): Mus musculus

PROVIDER: GSE127488 | GEO | 2020/02/05

REPOSITORIES: GEO

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Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium[organoids RNA-seq]

Project description:Smarcad1 is one of the most conserved chromatin remodelling factors, from yeast to human, with suggested functions in gene silencing, heterochromatin maintenance and genome stability. However, its role in tissue function is poorly understood. As this factor is highly expressed in the stem- and proliferative zone in the intestinal epithelium, we explored the role of this factor in this tissue. Intestine tissue-specific deletion of Smarcad1 resulted in notable changes in gene expression in the small intestine, colon and organoids from small intestine. Strikingly, we found an increase of expression of several genes linked to innate immunity and a dramatic increase of a Bglap3 coding for an osteocalcin isoform, a protein normally expressed in osteoblasts.

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Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium[SI RNA-seq]

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Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [Cocr RNA-seq]

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Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [wCO RNA-seq]

Project description:Smarcad1 is one of the most conserved chromatin remodelling factors, from yeast to human, with suggested functions in gene silencing, heterochromatin maintenance and genome stability. However, its role in tissue function is poorly understood. As this factor is highly expressed in the stem- and proliferative zone in the intestinal epithelium, we explored the role of this factor in this tissue. Specific deletion of Smarcad1 in the intestinal epithelium led to colitis resistance in the dextran sodium sulphate colitis model. Intestine tissue-specific deletion of Smarcad1 resulted in notable changes in gene expression in the small intestine, colon and organoids from small intestine. Strikingly, we found an increase of expression of several genes linked to innate immunity. Our study demonstrates that an innate immunity response can be coordinated by a chromatin remodelling factor. It highlights the role of intestinal epithelial cells in the colitis response and we identified candidate members of the gut microbiome that elicit an epithelial Smarcad1-dependent colitis response.

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Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [ChIP-seq]

Project description:How intestinal epithelial cells interact with the host immune system and the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is one of the most conserved chromatin remodelling factors, from yeast to human, with suggested functions in gene silencing, heterochromatin maintenance and genome stability. However, its role in tissue function is poorly understood. As this factor is highly expressed in the stem- and proliferative zone in the intestinal epithelium, we explored the role of this factor in this tissue. Specific deletion of Smarcad1 in the intestinal epithelium led to colitis resistance in the dextran sodium sulphate colitis model. Intestine tissue-specific deletion of Smarcad1 resulted in notable changes in gene expression in the small intestine and colon. Absence of Smarcad1 led to changes in chromatin accessibility and significant changes in histone H3K9me3 but not H3K9me2 over many sites, including many genes that are differentially regulated upon Smarcad1 deletion. Our study demonstrates that an innate immunity response can be coordinated by a chromatin remodelling factor.

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Smarcad1 coordinates innate immunity-linked gene expression in the intestinal epithelium [ATAC-seq]

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Smarcad1 mediates microbiota-induced inflammation by coordinationg gene expression in the intestinal epithelium [H3K9me3 ChIP-seq]

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High-throughput sequence data of ChIP performed with anti-SMARCAD1 (ASNA) or anti-CBP actibodies.

Project description:Histone acetylation and nucleosome remodeling play a pivotal role in transcriptional regulation. While histone acetylase and ATP-dependent chromatin remodeling activities have been well characterized, how the two activities are coordinated remains to be uncovered. We discovered ATP-dependent histone H2A acetylation activity in Drosophila nuclear extracts. This activity was column-purified and demonstrated to be composed of CBP and SMARCAD1, which belongs to the Etl1 subfamily of the Snf2 family of helicase-related proteins. SMARCAD1 enhanced acetylation of H2A K5 and K8 by CBP in nucleosomes in an ATP-dependent fashion. Expression array analysis of S2 cells having ectopically expressed SMARCAD1 revealed up-regulated genes. Using native genome templates of these up-regulated genes, we found that SMARCAD1 activates their transcription in vitro. Knockdown analysis of SMARCAD1 and CBP indicated overlapping gene control, and ChIP-seq analysis of these commonly controlled genes showed that CBP is recruited to the promoter prior to SMARCAD1. Moreover, Drosophila genetic experiments demonstrated interaction between SMARCAD1/Etl1 and CBP/nej during development. The interplay between the remodeling activity of SMARCAD1 and histone acetylation by CBP sheds light on chromatin and the genome-integrity network. Examination of 2 different protein in 1 cell type.

2016-03-17 | E-GEOD-72666 | biostudies-arrayexpress

ChIP-Seq of chromatin remodeler SMARCAD1 and H3K9me3 in female mouse embryonic stem cells (PGK12.1 XX)

Project description:Investigation of the co-occurance of the ATP-dependent chromatin remodeler SMARCAD1 and the histone modification H3K9me3 in the genome of PGK12.1 XX ES cells. ChIP-seq of endogenous SMARCAD1 was carried out in control and SMARCAD1-knockdown ES cells using a double crosslinking procedure. Additionally, H3K9me3 ChIP-seq was performed in double-cross linked control PGK12.1 XX cells. Input samples and precipitates with an IgG antibody were sequenced (Illumina HiSeq1500) as controls. Antibodies used were SMARCAD1 PAB15737 (Abnova) and H3K9me3 ab8898 (abcam).

2019-02-17 | E-MTAB-7012 | biostudies-arrayexpress

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