CXXC finger protein 1 is critical for T cell intrathymic development through regulating H3K4 trimethylation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Lai Wei
PROVIDER: E-GEOD-79976 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:While histone H3 lysine 27 trimethylation (H3K27Me3) is associated with gene silencing, whether H3K27Me3 demethylation affects transcription and cell differentiation in vivo has remained elusive. To investigate this, we conditionally inactivated the two H3K27Me3 demethylases, Jmjd3 and Utx, in non-dividing intrathymic CD4+ T cell precursors. We show that both enzymes redundantly promote H3K27Me3 removal at, and expression of, a specific subset of genes involved in terminal thymocyte differentiation, especially S1pr1, encoding a sphingosine-phosphate receptor required for thymocyte egress. Floxed alleles of the genes encoding Utx and Jmjd3 (Kdm6a and Kdm6b, respectively) were deleted in double positive (DP) thymocytes carrying a CD4 Cre transgene. Genome-wide H3K27Me3 ChipSeq was performed on (i) pre-selection (CD69lo) DP thymocytes from wild-type mice carrying an endogenous polyclonal TCR repertoire, (ii) mature (TCRhi CD24lo) CD4 SP thymocytes from wild type (Wt), Jmjd3KO, UtxKO and dKO mice carrying an endogenous polyclonal TCR repertoire and (iii) mature (Va2hi CD24lo) CD4 SP thymocytes from wild type and dKO mice carrying the OTII TCR transgene.
2015-09-02 | E-GEOD-70795 | biostudies-arrayexpress
Project description: Not available
| S-EPMC4879243 | biostudies-literature
Project description:H3K27Ac ChIP-seq in wild type and cohesin-deficient thymocytes Rad21 was deleted in CD4+ CD8+ double positive (DP) thymocytes by crossing a Rad21 floxed allele with a Cd4-driven Cre transgene. DP positive thymocytes were FACS-sorted from control and Rad21-/- littermates, which were then used to perform chromatin immunoprecipitation for histone H3 acetylated on lysine 27 (H3K27Ac).
2015-02-12 | E-GEOD-61428 | biostudies-arrayexpress
Project description: Not available
| S-EPMC3740882 | biostudies-literature
Project description:To characterize the largely unknown functions of oxidised methylcytosines (oxi-mC; 5hmC/5fC/5caC) in DNA, several sequencing protocols have been recently developed. Quantitative analysis is complicated because DNA methylation modifications need to be deconvoluted from the data which is affected by several experimental parameters, including e.g. imperfect bisulphite conversion, oxidation efficiencies, various chemical labeling and protection steps, and sequencing errors. Here, we present a hierarchical generative model, Lux, for integrative analysis of any combination of BS-seq and âoxi-mCâ-seq (BS-seq/oxBS-seq/TAB-seq/fCAB-seq/CAB-seq/redBS-seq/MAB-seq) data. We show that Lux improves quantification and comparison of methylation levels over existing methods and that Lux can easily process any oxi-mC-seq data sets to quantify all cytosine modifications simultaneously together with their experimental parameters. Application of Lux to targeted data from Tet2 knockdown ESCs and T cells during development demonstrates DNA modification quantification at unprecedented detail, quantifies active demethylation pathway and reveals 5hmC localization in putative regulatory regions. Examine the distribution of C, 5mC, and 5hmC in DP, CD4 SP, and naïve CD4 T cells within selected loci. Half of the samples are measured using the traditional bisulphite-seq protocol but the other half is measured using the oxidative bisulphite-seq protocol (oxBS-seq).
2016-07-03 | E-GEOD-68575 | biostudies-arrayexpress
Project description:Here we developed CapStarr-Seq, a novel high-throughput strategy to quantitatively assess enhancer activity in mammals. This approach couples capture of regions of interest to previously developed Starr-seq technique. Extensive assessment of CapStarr-seq demonstrated accurate quantification of enhancer activity. Furthermore, we found that enhancer strength correlates with binding complexity of tissue-specific transcription factors and super-enhancers, while additive enhancer activity isolates key genes involved in cell identity and function. ChIP-seq for the transcription factors HEB and TCF1, the DNaseI and the epigenetic modification H3K9me3 in DP thymocytes.
2015-04-09 | E-GEOD-63732 | biostudies-arrayexpress
Project description:Genomic instability associated with DNA replication stress is linked to cancer and genetic pathologies in humans. If not properly regulated, replication stress, such as fork stalling and collapse, can be induced at natural replication impediments present throughout the genome. The fork protection complex (FPC) is thought to play a critical role in stabilizing stalled replication forks at several known replication barriers including eukaryotic rDNA genes and the fission yeast mating-type locus. However, little is known about the role of the FPC at other natural impediments including telomeres. Telomeres are considered to be difficult to replicate due to the presence of repetitive GT-rich sequences and telomere-binding proteins. However, the regulatory mechanism that ensures telomere replication is not fully understood. Here, we report the role of the fission yeast Swi1/Timeless, a subunit of the FPC, in telomere replication. Loss of Swi1 causes telomere shortening in a telomerase-independent manner. Our epistasis analyses suggest that heterochromatin and telomere-binding proteins are not major impediments for telomere replication in the absence of Swi1. Instead, repetitive DNA sequences impair telomere integrity in swi1Î mutant cells, leading to the loss of repeat DNA. In the absence of Swi1, telomere shortening is accompanied with an increased recruitment of Rad52 recombinase and more frequent amplification of telomere/subtelomeres, reminiscent of tumor cells that utilize the alternative lengthening of telomeres pathway (ALT) to maintain telomeres. These results suggest that Swi1 ensures telomere replication by suppressing recombination and repeat instability at telomeres. Our studies may also be relevant in understanding the potential role of the FPC in regulation of telomere stability in cancer cells. Genome-wide distributions of Rad52 in wild type and in swi1 deletion in fission yeast The'SP1173_WT ChIP-seq' is an input sample (non-tagged data).
2016-02-25 | E-GEOD-74487 | biostudies-arrayexpress
Project description:miR-181a1/b1, miR-181a2/b2, and miR-181c/d belong to a highly conserved family of microRNA clusters, yet their role in vivo is poorly understood. Here we show that the miR-181a1/b1 cluster is absolutely essential for NKT development and is a critical determinant of thymocyte proliferation, survival and T-cell receptor α locus rearrangement. Furthermore, while individual ablation of miR-181a2/b2 and miR-181c/d revealed no overt phenotypes, compound mutant mice lacking both miR-181a1/b1 and miR-181a2/b2 display decreased survival, reduced body weight, and abnormal B cell development. Mechanistically, we reveal that miR-181 regulates PTEN, a key tumor suppressor whose abundance determines key metabolic adaptations required to meet the biosynthetic demands of highly proliferative tissues. These results provide important insights into the physiological function of this family of microRNAs in vivo; moreover, it places miR-181 as a central regulator of the PI3K signaling pathway and cellular metabolism. Three sorted populations of double positive (DP) thymocytes from each of two conditions (WT and miR181a1/b1 -/- mice)
2014-04-09 | E-GEOD-41090 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7684838 | biostudies-literature
Project description: Not available
| S-EPMC3350864 | biostudies-literature