Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Master Cistromic Circuit Governing Hepatic Fibrogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Rattus norvegicus Homo sapiens

PROVIDER: GSE41580 | GEO | 2013/04/29

SECONDARY ACCESSION(S): PRJNA177566

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

A Master Cistromic Circuit Governing Hepatic Fibrogenesis

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-04-29 | E-GEOD-41580 | biostudies-arrayexpress

A master cistromic circuit governing hepatic fibrogenesis [ChIP-seq]

Project description:Liver fibrosis is a reversible wound-healing response to liver injury and hepatic stellate cells (HSCs) are central cellular players that mediate hepatic fibrogenesis. However, the molecular mechanisms that govern this process remain unclear. Here, we reveal a novel cistromic circuit in HSCs comprising the vitamin D receptor (VDR) and SMAD transcription factors that restrains the intensity of hepatic fibrogenesis. Ligand-activated VDR suppresses TGFβ1-induced pro-fibrotic gene expression in HSCs. Administration of a vitamin D analogue, calcipotriol, diminishes the fibrotic response in a mouse model of liver fibrosis, while VDR knockout mice spontaneous develop extensive hepatic fibrosis by age 6 months. Using ChIP-Seq, we find that the anti-fibrotic properties of VDR are due to crosstalk with SMAD, mediated by their co-occupancy of DNA-binding sites on pro-fibrotic genes. Specifically, SMAD binding potentiates local chromatin accessibility to enhance VDR recruitment at the same cis-regulatory elements, which reciprocally antagonizes the interaction between SMAD3 and chromatin and limits the assembly of transcriptional activation complexes at fibrotic genes, a process that is enhanced by the presence of VDR agonists. These results not only establish this coordinated VDR/SMAD cistromic circuit as a master regulator of hepatic fibrogenesis, but also support VDR as a potential drug target to ameliorate liver fibrosis. Identification of VDR, SMAD3 and H3 binding sites in human stellate LX2 cells that were pre-treated with calcipotriol (100nM) for 16 hrs (where calcipotriol treatment is indicated) followed by incubation of calcipotriol (100nM) or TGFβ1 (1ng/ml) for another 4 hours (where indicated).

2013-04-29 | E-GEOD-38103 | biostudies-arrayexpress

A master cistromic circuit governing hepatic fibrogenesis [expression array]

2013-04-29 | E-GEOD-41579 | biostudies-arrayexpress

A master cistromic circuit governing hepatic fibrogenesis [ChIP-seq]

2013-04-29 | GSE38103 | GEO

A master cistromic circuit governing hepatic fibrogenesis [expression array]

2013-04-29 | GSE41579 | GEO

Matrix stiffness modulates fibrogenesis in hepatic stellate cells through AP-1-induced chromatin priming

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-01 | GSE220703 | GEO

INO80 complex in the core regulatory network governing ESC self-renewal

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series