Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA296598 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Macrophage activation during the innate immune response is tightly regulated to prevent tissue damage while activating the defense to cellular attack. Using a mouse model where Trim33 is specifically deleted in mature myeloid cells, we show that TRIM33 is essential for two aspects of the inflammatory response in vivo. Loss of TRIM33 attenuates the initiation of macrophage activation by lipopolysaccharide (LPS) and TRIM33 is necessary to switch off transcription of inflammatory genes during late stages of LPS activation. Using chromatin immunoprecipitation coupled to deep sequencing, we provide a link between TRIM33 binding, RNA Polymerase II occupancy and H3K4me3 spreading on inflammatory genes in macrophages and reveal novel insights concerning the transcriptional regulation of Ifn-beta where TRIM33 exerts a repressive function via a distal regulatory region during late stages of LPS activation of macrophages. These findings pinpoint TRIM33 as a major regulator of the resolution of inflammation and indicate that transcriptional regulators can fine-tune H3K4me3 spreading. To study the role of TRIM33 in the transcriptional response induced by pathogen receptors, we analyzed whether lack of TRIM33 in macrophages affected the TLR-mediated regulation of proinflammatory and antimicrobial genes. To study this role, we bred TRIM33fl/fl mice with Lyz-Cre mice (obtained from The Jackson Laboratory, Bar Harbor, Maine, USA) where the Cre recombinase gene is under the regulatory sequences of the Lyz gene that is expressed only in mature myeloid cells. Bone marrow cells from 2 LyzCre/Trim33+/+ mice and 2 LyzCre/Trim33flox/flox mice were then differentiated in macrophages and treated during 0h, 4h, 12h and 24h with LPS. Total RNA was extracted from macrophages and analysed using cDNA microarrays. The set of gene expression consists of 16 samples of RNA of bone marrow derived macrophages activated with 100ng/ml of LPS during 0h, 4h, 12h, 24h, 8 samples from 2 LyzCre/Trim33+/+ mice and 8 samples from 2 LyzCre/Trim33flox/flox mice.
2015-06-30 | E-MTAB-1441 | biostudies-arrayexpress
Project description:Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-b gene (Ifnb1) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results in high-sustained expression of Ifnb1 at late stages of toll-like receptor-mediated activation in macrophages but not in fibroblasts. In macrophages, TRIM33 is recruited by PU.1 to a conserved region, Ifnb1 Control Element (ICE), located 15kb upstream of the Ifnb1 transcription start site. ICE constitutively interacts with Ifnb1 through a TRIM33-independent chromatin loop. At late phases of lipopolysaccharide activation of macrophages, TRIM33 is bound to ICE, regulates Ifnb1 enhanceosome loading, controls Ifnb1 chromatin structure, and represses Ifnb1 gene transcription by preventing recruitment of CBP/p300. These results characterize a previously unknown mechanism of macrophage-specific regulation of Ifnb1 transcription whereby TRIM33 is critical for Ifnb1 gene transcription shut down.
2015-11-18 | GSE73322 | GEO
Project description:Dynamics of TRIM33 binding in macrophages and effects of TRIM33 deletion on chromatin state during activation of primary macrophages.
| PRJNA186942 | ENA
Project description:Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription
| PRJNA211259 | ENA
Project description:To get insight into TRIM33 functions, TRIM33 ChIP-seq was carried out in murine macrophage cell line (RAW) and in bone marrow-derived macrophages (BMDM). The results showed that, in addition to its role in hematopoietic differentiation, TRIM33 may modulate PU.1 transcriptional activity during macrophage development and/or activation.To characterize the role of TRIM33 in macrophages, we bred TRIM33fl/fl mice with Lyz-Cre mice where the Cre recombinase gene is under the regulatory sequences of the Lyz gene that is expressed only in mature myeloid cells. Bone marrow cells from LyzCre/Trim33+/+ mice and LyzCre/Trim33flox/flox mice were differentiated in macrophages and treated during 0h, 4h, 12h and 24h with LPS. Using ChIP-seq, we provide a link between TRIM33 binding and H3K4me3 spreading on inflammatory genes in macrophages. Chromatin immunoprecipitations of TRIM33 and H3K4Me3 followed by multiparallel sequencing performed in murine bone marrow-derived macrophages (BMDM).
2015-11-23 | E-GEOD-43654 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:The replication timing program, or the order in which DNA is duplicated during S-phase, is associated with various features of chromosome structure and function, including gene expression, histone modifications, and 3-D compartmentalization of chromatin.
2013-04-16 | GSE45716 | GEO
Project description: Not available
| S-EPMC395764 | biostudies-literature
Project description: Not available
| S-EPMC4490682 | biostudies-literature
Project description:To get insight into TRIM33 functions, TRIM33 ChIP-seq was carried out in murine macrophage cell line (RAW) and in bone marrow-derived macrophages (BMDM). The results showed that, in addition to its role in hematopoietic differentiation, TRIM33 may modulate PU.1 transcriptional activity during macrophage development and/or activation.To characterize the role of TRIM33 in macrophages, we bred TRIM33fl/fl mice with Lyz-Cre mice where the Cre recombinase gene is under the regulatory sequences of the Lyz gene that is expressed only in mature myeloid cells. Bone marrow cells from LyzCre/Trim33+/+ mice and LyzCre/Trim33flox/flox mice were differentiated in macrophages and treated during 0h, 4h, 12h and 24h with LPS. Using ChIP-seq, we provide a link between TRIM33 binding and H3K4me3 spreading on inflammatory genes in macrophages.
2015-11-23 | GSE43654 | GEO