mavii

This gene configuration precedes or is coincidental with an enhancer-dependent level of compaction established by enhancer-promoter contacts (and which could also be facilitated by CTCF/cohesin-mediated loops) to create an RC that promotes germline transcription and V(D)J recombination at the appropriate thymocyte stage [23,36,52,60,70,72,75,76 ...

CTCF has it all. The transcription factor binds to tens of thousands of genomic sites, some tissue-specific, others ultra-conserved. It can act as a transcriptional activator, repressor and insulator, and it can pause transcription. ... Seitan VC, et al. 2011. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation.

The architectural protein CTCF regulates the conformation and recombination of antigen receptor loci. To study the importance of CTCF in Tcrb locus repertoire formation, we created a conditional knockout mouse line that deletes Ctcf early during thymocyte development. We observed an incomplete block in thymocyte development at the double-negative to double-positive transition, resulting in ...

Germline deletion of TCF-1 leads to a severe reduction in thymocyte numbers (Verbeek et al., 1995). Although some T lineage-like cells continue to develop in the thymus of Tcf7-deficient mice, ... The distance between TCF-1 and CTCF (serving as control) ChIP-seq summits and the closest nucleosome summits were calculated as an alternative ...

More studies are necessary to find out whether the actions of CTCF during thymocyte development are also dependent on formation of loops. One recent finding shows that indeed TCR diversities might be influenced by CTCF looping 75. Notably, CTCF is not the only chromatin structure modifier playing a role in T-cell development.

This study is one of many showing that CTCF functions as a chromatin organizer and transcriptional regulator genome-wide. However, detailed understanding of the impact of specific CBEs is needed to fully comprehend the biological function of CTCF and how CTCF influences the generation of the TCR repertoire during thymocyte development.

CTCF binding sites in Tcrb are shown in Fig. 3A (top) as established by ChIP-seq data from RAG-deficient DN thymocytes . ... Alterations in Tcrb conformation do not require extensive thymocyte proliferation (A) Representative FACS analysis of thymocytes from mice with the indicated genotypes. Cells were stained with CD4-PE and CD8-FITC.

Characterization of CTCF-deleted thymocytes. (A) Expression of ISP cell markers. Flow cytometric analyses of HSA, CD3, TCR, CD5 and CD69 in thymocyte subpopulations, displayed as overlays of wild ...

Xue and colleagues show that Tcf1 and Lef1 recruit the genome organizer CTCF to promote chromatin interactions and form highly connected, dynamic interaction hubs in CD8+ T cells undergoing ...

To understand CTCF function in vivo, we generated a condi-tional Ctcf allele (Ctcff) by inserting loxP sites upstream of exon 3 and downstream of exon 12 (Figure 1A). Equivalent levels of CTCF are expressed in Ctcff/f and wild-type mice (data not shown). Ctcf þ/f mice were crossed with mice expressing Cre recombinase ubiquitously (Sakai and ...

Consistent with a previous report, we find that ubiquitous ablation of the Ctcf gene results in early embryonic lethality. Tissue‐specific inactivation of CTCF in thymocytes specifically hampers the differentiation of αβ T cells and causes accumulation of late double‐negative and immature single‐positive cells in the thymus of mice.

Red and blue bars denote the position of a thymocyte-specific domain formed around the Runx1 gene, with a thymocyte-specific boundary corresponding to increased CTCF binding denoted by an asterisk. Triangles denote the orientation of the CTCF motifs at the border of this thymocyte-specific spatial chromatin domain. Source data available in S1 ...

The architectural protein CTCF regulates the conformation and recombination of Ag receptor loci. To study the importance of CTCF in Tcrb locus repertoire formation, we created a conditional knockout mouse line that deletes Ctcf early during thymocyte development. We observed an incomplete block in thymocyte development at the double-negative to double-positive transition, resulting in greatly ...

By contrast, CTCF occupancy at +1kb (located in the first intron of Ifng and corresponding to DHSII) and at +66kb (the mouse ortholog of human DHS+119kb) was somewhat above background in naïve CD4+ T cells, and was clearly and selectively increased in Th1 but not Th2 cells. CTCF occupancy was not detected at the −22kb and +29kb enhancers ...

a, Thymocyte differentiation from left to right: CD4 − CD8 − DN stages 1 to 4; CD4 + CD8 + DP, CD4 + CD8 lo; CD4 or CD8 SP cells.Proliferation is in green, cell cycle arrest in red. Histograms ...

Taken together, our results show that CTCF is required in a dose-dependent manner and is involved in cell cycle progression of alphabeta T cells in the thymus. We propose that CTCF positively regulates cell growth in rapidly dividing thymocytes so that appropriate number of cells are generated before positive and negative selection in the thymus.

Abstract. The architectural protein CTCF regulates the conformation and recombination of Ag receptor loci. To study the importance of CTCF in Tcrb locus repertoire formation, we created a conditional knockout mouse line that deletes Ctcf early during thymocyte development. We observed an incomplete block in thymocyte development at the double-negative to double-positive transition, resulting ...

a) Thymocyte differentiation from left to right: CD4 − CD8 − double negative (DN) stages 1 to 4; CD4 + CD8 + double positive (DP), CD4 + 8 lo; CD4 or CD8 single positive (SP) cells.Proliferation is in green, cell cycle arrest in red. Histograms show DNA content. b) Conditional Rad21 allele (see supplementary fig. 1a).. c) Real time genomic PCR of Rad21 locus deletion, RT-PCR of Rad21 RNA ...