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Effect of ZBTB18 on gene expression and chromatin organization [ATAC-seq]

ABSTRACT: Effect of ZBTB18 on gene expression and chromatin organization [ATAC-seq]

PROVIDER: PRJNA802666 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17852733_1.fastq.gz	Fastqsanger.gz
	SRR17852733_2.fastq.gz	Fastqsanger.gz
	SRR17852734_1.fastq.gz	Fastqsanger.gz
	SRR17852734_2.fastq.gz	Fastqsanger.gz
	SRR17852735_1.fastq.gz	Fastqsanger.gz

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Effect of ZBTB18 on gene expression and chromatin organization [ATAC-seq]

Project description:This study set out to delineate gene expression programs that are differentially modulated in metastatic breast cancer cells with high versus low ability to further metastasize. To this end, the gene expression profiles of E0771GFP cells, M11GFP and M12GFP cells were determined. Analysis of these data sets identified ZBTB18 as a transcriptional repressor with lower activity in tumor cells that retain a high metastatic potential. To determine how ZBTB18 affects gene expression and chromatin organization, ZBTB18 was overexpressed in E0771GFP breast cancer cells. Gene expression profiles and differentially accessible DNA regions analyses were performed and identified Tgfbr2 as one of the genes most significantly repressed by ZBTB18. To determine the contribution of the TGFb1 -TGFBR2 signaling axis towards ZBTB18-mediated effects, E0771GFP cells overexpressing ZBTB18 were transduced with a doxycycline-inducible Tgfbr2 construct. These cells were then treated with doxycycline and recombinant TGFb1 or vehicle control and gene expression profiles were determined. These studies revealed that inhibition of ZBTB18 activity in tumor cells promotes metastasis by increasing chromatin accessibility and by enabling pro-metastatic TGFb1-TGFBR2-driven changes.

2022-12-22 | GSE195941 | GEO

Effect of ZBTB18 on gene expression and chromatin organization

Project description:Effect of ZBTB18 on gene expression and chromatin organization

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Effect of ZBTB18 on gene expression and chromatin organization [RNA-seq]

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Effect of ZBTB18 on gene expression and chromatin organization [RNA-seq]

Project description:Effect of ZBTB18 on gene expression and chromatin organization [RNA-seq]

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The chromatin landscape modified by Zbtb18 in activated B cells

Project description:The differentiation of plasma cell is prescisely controlled by the key transcriptional program as well as epigenetic changes. Recently, we have identified, one zinc finger protein, Zbtb18, as a new regulator for B cell differentiation process. To investigate the molecular mechanisms of Zbtb18 during B cell differentiation program we employed the assay for transposase (Tn5) -accessible chromatin followed by deep sequencing (ATAC-Seq) in the sorted Control and Zbtb18 over-expressing B cells (B220+ CD138-) before and after anti-CD40 and IL-4 stimulation. Mice primary B cells were retrovially transduced with either control vector with RFP repoter or Zbtb18 with GFP repoter, and both were primed 2 days on the 40LB stroma cells before mixed 1:1 and then stimulated with anti-CD40 (10ug/ml) and IL-4 (10ng/ml) for 2 days. Activated B cells, B220+ CD138-, were sorted by BD AriaIII and followed by ATAC-seq protocol (Nat Methods. 2017 Oct;14(10):959-962).

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Project description:The intracellular O-linked N-acetylglucosamine (O-GlcNAc) modification is known to be enriched in the nucleus and in particular on chromatin, but many of its chromatin targets remain to be identified. Herein we demonstrate the O-GlcNAcylation of YEATS Domain Containing 2 (YEATS2), a subunit of the chromatin Ada-two-A-containing (ATAC) complex and a reader of histone H3K27ac. We show that YEATS2 interacts with the O-GlcNAc transferase (OGT) and further pinpoint its major O-GlcNAcylation site to be Thr604 using electron transfer dissociation mass spectrometry. O-GlcNAcylation promotes the chromatin association of YEATS2, and the affinity between YEATS2 and other ATAC components on chromatin, such as ZZZ3, GCN5 and PCAF. Downstream, YEATS2-T604A attenuated the ATAC-dependent histone H3K9ac levels and inactivated the expression of essential ribosomal genes as shown in chromatin immunoprecipitation assays. Further, xenograft experiments show that YEATS2 O-GlcNAcylation promotes lung cancer tumorigenesis. Our work reveals the critical role of YEATS2 O-GlcNAcylation in stabilizing the ATAC complex on chromatin and expands the chromatin substrates of OGT.

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Project description:ZBTB18 is a transcriptional repressor and tumor suppressor in glioblastoma (GBM). Specifically, it acts as a repressor of mesenchymal genes. ZBTB18 interacts with C-terminal binding proteins 1 and 2 through a VLDL motif. In GBM, ZBTB18 is cleaved the the calpain 2 intracellular proteases which generates truncated Nte and Cte short forms. Here we have investigated gene expression changes which occur upon the expression of ZBTB18 full lenght or ZBTB18 short form Nte (SF-Nte), as well as upon expression of the mutated counterparts which no longer interacts with CTBP1/2.

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