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Time series RNA-seq of Th1 differentiation: The effect of Progesterone on Th1 differentiation?

ABSTRACT: T-helper 1 responses are involved in the development of many autoimmune diseases such as Multiple sclerosis (MS). MS is a relapse remitting disease that eventually progresses to a progressive neurodegenerative disease. During pregnancy the relapse rate of MS is significantly reduced with peak reduction during the third trimester followed by an increase in relapse rate post-partum. One of the highest expressed hormones during pregnancy is progesterone. Progesterone has been show to have an inhibiting effect on T-cell activation and been proposed to promote a T-regulatory like cell state. To evaluate the influence of progesterone on the chromatin and gene expressive state of T-helper type 1 cells we differentiated primary human naïve T-cell in the presence progesterone with sampling at 0.5, 1, 2, 6 and 24 hours and performed ATAC-seq and RNA-seq.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo sapiens

SUBMITTER: Olof Rundquist

PROVIDER: E-MTAB-10423 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Using high-throughput multi-omics data to investigate structural balance in elementary gene regulatory network motifs.

Zenere Alberto A Rundquist Olof O Gustafsson Mika M Altafini Claudio C

Bioinformatics (Oxford, England) 20211201 1

<h4>Motivation</h4>The simultaneous availability of ATAC-seq and RNA-seq experiments allows to obtain a more in-depth knowledge on the regulatory mechanisms occurring in gene regulatory networks. In this article, we highlight and analyze two novel aspects that leverage on the possibility of pairing RNA-seq and ATAC-seq data. Namely we investigate the causality of the relationships between transcription factors, chromatin and target genes and the internal consistency between the two omics, here m ...[more]

PMID: 34383882

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Time series ATAC-seq of Th1 differentiation: The effect of Progesterone on Th1 differentiation?

Project description:T-helper 1 responses are involved in the development of many autoimmune diseases such as Multiple sclerosis (MS). MS is a relapse remitting disease that eventually progresses to a progressive neurodegenerative disease. During pregnancy the relapse rate of MS is significantly reduced with peak reduction during the third trimester followed by an increase in relapse rate post-partum. One of the highest expressed hormones during pregnancy is progesterone. Progesterone has been show to have an inhibiting effect on T-cell activation and been proposed to promote a T-regulatory like cell state. To evaluate the influence of progesterone on the chromatin and gene expressive state of T-helper type 1 cells we differentiated primary human naïve T-cell in the presence progesterone with sampling at 0.5, 1, 2, 6 and 24 hours and performed ATAC-seq and RNA-seq.

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2019-03-15 | E-MTAB-7661 | biostudies-arrayexpress

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IL6-regulated CDk8-mediated phosphoproteome of human primary Th1 cells

Project description:Cytokines are highly pleiotropic ligands that critically contribute to a balanced immune response. We have an incomplete understanding of how cytokines elicit their functional pleiotropy, which has limited their therapeutic efficacy. Here, using Interleukin-6 (IL-6) as a model system, we have performed detailed phosphoproteomic and transcriptomic studies in human CD4 + T helper (Th)-1 cells to address the molecular bases defining cytokine functional pleiotropy. We have identified cyclin dependent kinase (CDK)8 as a new negative regulator of transcriptional activities of signal transducer and activator of transcription (STAT)3. We found that CDK8 is a major regulator of the IL-6 phosphoproteome and interacts with STAT3 in the nucleus upon IL-6 stimulation. Inhibition of CDK8 activity, using specific small molecules inhibitors, reduced the IL-6-induced phosphoproteome by 23% in Th-1 cells, including STAT3 S727 phosphorylation. STAT3 binding to target DNA sites in the genome was increased upon CDK8 inhibition, which resulted in a concomitant increase in STAT3 mediated transcriptional activity. Importantly, inhibition of CDK8 activity under Th-17 polarizing conditions resulted in an enhancement of Th-17 differentiation. Our results support a model where CDK8 regulates STAT3 transcriptional processivity via modulation of its gene loci resident time, critically contributing to diversification of IL-6 responses.

2020-12-23 | PXD020964 | Pride

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