The effect of Bcl6 on the liver sex difference
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE89091 | GEO | 2017/01/19
SECONDARY ACCESSION(S): PRJNA350259
REPOSITORIES: GEO
Similar Datasets
Project description:To confirm the effect of Bcl6 on the liver sex difference, we performed the gene expression analysis in male and female wild type mice and male and female liver specific Bcl-6 deficient mice.
2017-11-29 | GSE107435 | GEO
Project description:Sex-dependent pituitary growth hormone (GH) secretory patterns determine the sex-biased expression of >1,000 genes in mouse and rat liver, affecting lipid and drug metabolism, inflammation and disease. A fundamental biological question is how robust differential expression can be achieved for hundreds of sex-biased genes simply based on the GH input signal pattern: pulsatile GH stimulation in males vs. near-continuous GH exposure in females. STAT5 is an essential transcriptional mediator of the sex-dependent effects of GH in the liver, but the mechanisms that underlie its sex-dependent actions are obscure. Here we elucidate the dynamic, sex-dependent binding of STAT5 and the GH/STAT5-regulated repressor BCL6 to mouse liver chromatin, revealing the counteractive interplay between these two regulators of liver sex-specificity. Our findings establish a close correlation between sex-dependent STAT5 binding and sex-biased target gene expression. Moreover, sex-dependent STAT5 binding correlated positively with sex-biased DNase hypersensitivity and H3-K4me1 and H3-K4me3 (activating) marks, correlated negatively with sex-biased H3-K27me3 (repressive) marks, and was associated with sex-differentially enriched motifs for HNF6/CDP factors. Importantly, BCL6 binding was preferentially associated with repression of female-biased STAT5 targets in male liver. Furthermore, BCL6 and STAT5 common targets but not BCL6 unique targets showed strong enrichment for lipid and drug metabolism. These findings provide a comprehensive, genome-wide view of the mechanisms whereby these two GH-regulated transcription factors establish and maintain sex differences affecting liver physiology and disease. The approaches used here to characterize sex-dependent STAT5 and BCL6 binding can be applied to other condition-specific regulatory factors and binding sites and their interplay with co-operative chromatin-binding factors. Mouse livers were excised from individual male and female mice killed at either a peak of STAT5 binding activity, or during the growth hormone (GH) interpulse interval, when STAT5 activity is either low (females) or essentially undetectable (males). Sonicated, cross-linked liver nuclear chromatin was then used to identify STAT5 binding sites by ChIP-Seq.
2011-12-18 | E-GEOD-31578 | biostudies-arrayexpress
Project description:Hepatic gene expression shows sexual dimorphism. Here, we investigated the role of BCL6 in establishing sexually dimorphic chromatin state and performed H3K27ac ChIP-seq from livers of female and male Ctrl and BCL6 liver knock-out mice.
2022-10-21 | GSE138393 | GEO
Project description:Hepatic gene expression shows sexual dimorphism. Here, we investigated the role of BCL6 in establishing sexual dimorphism in hepatic gene expression and created Bcl6Flox/Flox,Alb-Cre mice and performed RNAseq from livers of 4- and 8-week-old male and female Ctrl and BCL6 liver knock-out mice.
2022-10-21 | GSE138391 | GEO
Project description:The effect of Bcl6 on liver sex difference
| PRJNA420073 | ENA
Project description:Sex-dependent pituitary growth hormone (GH) secretory patterns determine the sex-biased expression of >1,000 genes in mouse and rat liver, affecting lipid and drug metabolism, inflammation and disease. A fundamental biological question is how robust differential expression can be achieved for hundreds of sex-biased genes simply based on the GH input signal pattern: pulsatile GH stimulation in males vs. near-continuous GH exposure in females. STAT5 is an essential transcriptional mediator of the sex-dependent effects of GH in the liver, but the mechanisms that underlie its sex-dependent actions are obscure. Here we elucidate the dynamic, sex-dependent binding of STAT5 and the GH/STAT5-regulated repressor BCL6 to mouse liver chromatin, revealing the counteractive interplay between these two regulators of liver sex-specificity. Our findings establish a close correlation between sex-dependent STAT5 binding and sex-biased target gene expression. Moreover, sex-dependent STAT5 binding correlated positively with sex-biased DNase hypersensitivity and H3-K4me1 and H3-K4me3 (activating) marks, correlated negatively with sex-biased H3-K27me3 (repressive) marks, and was associated with sex-differentially enriched motifs for HNF6/CDP factors. Importantly, BCL6 binding was preferentially associated with repression of female-biased STAT5 targets in male liver. Furthermore, BCL6 and STAT5 common targets but not BCL6 unique targets showed strong enrichment for lipid and drug metabolism. These findings provide a comprehensive, genome-wide view of the mechanisms whereby these two GH-regulated transcription factors establish and maintain sex differences affecting liver physiology and disease. The approaches used here to characterize sex-dependent STAT5 and BCL6 binding can be applied to other condition-specific regulatory factors and binding sites and their interplay with co-operative chromatin-binding factors.
2011-12-18 | GSE31578 | GEO
Project description:Here, we investigated the role of BCL6 in hepatic response to E.Coli infection. Bcl6 F/F and Bcl6 F/F, Alb-Cre male and female mice were infected with E.Coli and livers were collected 24h after infection for RNAseq analysis.
2022-10-21 | GSE138392 | GEO
Project description:Animal models are important tools in scientific research, whereas the animals used are usually single-sex instead of mixed-sex in the experimental design. To better understand the effect of sex difference, we compared several phenotypes between male and female C57BL/6 mice, including behavioral tests, plasma corticosterone levels, adult neurogenesis, and RNA-seq. The experiments were performed under non-stressed and chronic-stressed conditions, respectively. Overall, our results showed several differences between male and female mice in sensorimotor performance while little difference was found in anxiety, depression, learning, and memory. We did not observe a significant difference in adult neurogenesis. There was a sex difference in plasma corticosterone levels under chronic stress conditions, either in 30 min after the restraint stress or after 60min of the recovery. Yet, the corticosterone levels were equivalent between the sexes under non-stressed conditions at any time point. Furthermore, the results of RNA-seq identified the differential expression genes between male and female mice under non-stressed or chronic-stressed conditions.
2022-08-22 | GSE211276 | GEO
Project description:Here, using ChIP-seq, we define the NF-κB cistrome which is comprised of 31,070 cis-acting binding sites responsive to LPS-induced signaling. In addition, we demonstrate that the transcriptional repressor B-cell lymphoma 6 (Bcl-6) regulates nearly a third of the Tlr4-regulated transcriptome and that 90% of the Bcl-6 cistrome is collapsed following Tlr4 activation. Bcl-6 deficient macrophages are acutely hypersensitive to lipopolysaccharide (LPS) and, using comparative ChIP-seq analyses, we find that the Bcl-6 and NF-κB cistromes intersect, within nucleosomal distance, at nearly half of Bcl-6 binding sites in stimulated macrophages to promote opposing epigenetic modifications of the local chromatin. These results reveal a genomic strategy for controlling the innate immune response in which repressive and inductive cistromes establish a dynamic balance between macrophage quiescence and activation via epigenetically marked cis-regulatory elements. keywords: Genome-wide location analysis Identification of BCL6 and NFkB binding sites in unstimulated and LPS-stimulated primary bone-marrow derived macrophages.
2010-11-24 | E-GEOD-16723 | biostudies-arrayexpress
Project description:We report that BCL6 interacts with BRD3 and that BRD3 inhibition upregulates BCL6. By obtaining sequence from chromatin immunoprecipitated DNA of A549 cells, we generated genome-wide binding gene spectrums of BCL6 and BRD3. By locating -3000 to +200 bps around TSS, we find that BRD3 binds to the promoters of 2470 genes and that BCL6 binds to the promoters of 694 genes, with 82 genes shared by BRD3 and BCL6. Interestingly, BCL6 itself is one of these 82 shared genes, implying that BCL6 mediated self-repression may require the participation of BRD3. Other shared genes includes SGK2, IDH2, HOXB6, SIRT1, SOCS3 and ZFNs, demonstrating the widely involvement of BRD3 in the regulatory role of BCL6. To examine the dependency of BCL6 on BRD3, we also compared BCL6-binding spectrums with or without a BET inhibitor, OTX015. The ChIP-seq data with BCL6 antibody exhibited a diverse BCL-binding spectrum composed of 731 genes in OTX015 treatment, with only 117 genes overlapped with that of DMSO treatment. These data demonstrates that BET inhibition is sufficient to change BCL6-binding spectrum. This study provides a new insight of BCL6 regulatory roles in KRAS-mutant NSCLCs, where BRD3 is recruited by BCL6 and affect BCL6 binding preference as a cofactor.
2018-09-13 | GSE119863 | GEO