Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE140363 | GEO | 2020/04/14
REPOSITORIES: GEO
Similar Datasets
Project description:Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation
| PRJNA589339 | ENA
Project description:BACKGROUND:Ubiquitously expressed CTCF is involved in numerous cellular functions, such as organizing chromatin into TAD structures. In contrast, its paralog, CTCFL, is normally only present in the testis. However, it is also aberrantly expressed in many cancers. While it is known that shared and unique zinc finger sequences in CTCF and CTCFL enable CTCFL to bind competitively to a subset of CTCF binding sites as well as its own unique locations, the impact of CTCFL on chromosome organization and gene expression has not been comprehensively analyzed in the context of CTCF function. Using an inducible complementation system, we analyze the impact of expressing CTCFL and CTCF-CTCFL chimeric proteins in the presence or absence of endogenous CTCF to clarify the relative and combined contribution of CTCF and CTCFL to chromosome organization and transcription. RESULTS:We demonstrate that the N terminus of CTCF interacts with cohesin which explains the requirement for convergent CTCF binding sites in loop formation. By analyzing CTCF and CTCFL binding in tandem, we identify phenotypically distinct sites with respect to motifs, targeting to promoter/intronic intergenic regions and chromatin folding. Finally, we reveal that the N, C, and zinc finger terminal domains play unique roles in targeting each paralog to distinct binding sites to regulate transcription, chromatin looping, and insulation. CONCLUSION:This study clarifies the unique and combined contribution of CTCF and CTCFL to chromosome organization and transcription, with direct implications for understanding how their co-expression deregulates transcription in cancer.
| S-EPMC7212617 | biostudies-literature
Project description:CTCF and CTCFL DNA binding profile in CTCFL induced and non-induced ES cells.CTCF is a highly conserved and essential zinc finger protein that in conjunction with cohesin organizes chromatin into loops, thereby regulating gene expression and epigenetic events. The function of CTCFL or BORIS, the testis-specific paralogue of CTCF, is less clear. Here, we show that CTCFL is only transiently present during spermatogenesis, prior to the onset of meiosis, when the protein co-localizes in nuclei with ubiquitously expressed CTCF. Our data show that CTCFL is functionally different from CTCF and its absence in mice causes sub-fertility due to a partially penetrant testicular atrophy. Genome-wide studies reveal that CTCFL and CTCF bind similar consensus sequences. However, only ~2000 out of the ~5,700 CTCFL and ~31,000 CTCF binding sites overlap. CTCFL binds promoters with loosely assembled nucleosomes, whereas CTCF favors consensus sites surrounded by phased nucleosomes. Thus, nucleosome dynamics specifies the genome-wide binding of CTCFL and CTCF. We propose that the transient expression of CTCFL in spermatogonia and preleptotene spermatocytes serves to occupy a subset of promoters and maintain the expression of male germ cell genes ChIP-seq for CTCF (with CTCF antibody) and CTCFL (with V5 antibody) in CTCFL_V5_GFP induced and non-induced ES cells
2012-07-25 | E-GEOD-34094 | biostudies-arrayexpress
Project description:CTCF and CTCFL DNA binding profile in CTCFL induced and non-induced ES cells.CTCF is a highly conserved and essential zinc finger protein that in conjunction with cohesin organizes chromatin into loops, thereby regulating gene expression and epigenetic events. The function of CTCFL or BORIS, the testis-specific paralogue of CTCF, is less clear. Here, we show that CTCFL is only transiently present during spermatogenesis, prior to the onset of meiosis, when the protein co-localizes in nuclei with ubiquitously expressed CTCF. Our data show that CTCFL is functionally different from CTCF and its absence in mice causes sub-fertility due to a partially penetrant testicular atrophy. Genome-wide studies reveal that CTCFL and CTCF bind similar consensus sequences. However, only ~2000 out of the ~5,700 CTCFL and ~31,000 CTCF binding sites overlap. CTCFL binds promoters with loosely assembled nucleosomes, whereas CTCF favors consensus sites surrounded by phased nucleosomes. Thus, nucleosome dynamics specifies the genome-wide binding of CTCFL and CTCF. We propose that the transient expression of CTCFL in spermatogonia and preleptotene spermatocytes serves to occupy a subset of promoters and maintain the expression of male germ cell genes
2012-07-25 | GSE34094 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE34091: Nucleosome dynamics specifies genome-wide binding of the male germ cell gene regulator CTCFL and of CTCF [Mouse430_2 Expression] GSE34092: Nucleosome dynamics specifies genome-wide binding of the male germ cell gene regulator CTCFL and of CTCF [MoGene-1_0 Expression] GSE34094: Nucleosome dynamics specifies genome-wide binding of the male germ cell gene regulator CTCFL and of CTCF [ChIP-Seq] Refer to individual Series
2012-07-24 | E-GEOD-34093 | biostudies-arrayexpress
Project description:The two paralogous zinc finger factors CTCF and CTCFL differ in expression such that CTCF is ubiquitously expressed, whereas CTCFL is found during spermatogenesis and in some cancer types. Both factors share the highly conserved DNA binding domain and are bound to DNA sequences with an identical consensus. Here we analyzed the differential gene expression effect mediated by expression of Ctcfl in undifferentiated and differentiated NIH3T3 cell.
2018-05-30 | GSE103196 | GEO
Project description:The two paralogous zinc finger factors CTCF and CTCFL differ in expression such that CTCF is ubiquitously expressed, whereas CTCFL is found during spermatogenesis and in some cancer types. Both factors share the highly conserved DNA binding domain and are bound to DNA sequences with an identical consensus. Here we analyzed the differential gene expression effect mediated by expression of Ctcfl in undifferentiated and differentiated p19 cell.
2018-05-30 | GSE103197 | GEO
Project description:Study of the differential binding behavior of the paralogous factors CTCF and CTCFL by ChIP-seq in mouse NIH3T3 and p19 cells.
2018-05-30 | GSE103198 | GEO
Project description:Ctcfl, a paralog of Ctcf, also known as BORIS (Brother of Regulator of Imprinted Sites), is a testis expressed gene whose function is largely unknown. As a cancer testis antigen, it is often expressed in tumor cells and also seen in two benign human vascular malformations, juvenile angiofibromas (JA) and infantile hemangiomas (IH). To better understand the function of Ctcfl we created tetracycline-inducible Ctcfl transgenic mice. We show that when Ctcfl expression is induced during embryogenesis, it results in intrauterine growth retardation, developmental eye malformations, multi-organ pathologies, vascular defects, and early neonatal lethality. This phenotype resembles prior mouse models which perturb the TGFB pathway. Embryonic stem cells with the Ctcfl transgene reproduce the same phenotype in ES cell: tetraploid chimeras. RNA-Seq of the Ctcfl ES cells revealed 14 genes, including a number of transcription factors/ co-activators, and signal transduction pathway genes that are significantly deregulated by Ctcfl expression. Bioinformatics analysis revealed the TGFB pathway to be most affected by embryonic Ctcfl expression. We propose that our transgenic mice reiterate a developmental program normally reserved for spermatogenesis that results in multiple organ pathology when expressed in embryogenesis as a result of the TGFB pathway dysregulation. Understanding of the phenotypic consequence of Ctcfl expression in non-testicular cells and elucidating downstream targets of Ctcfl has the potential to explain its role as a cancer testis antigen (CTA) and its involvement in two, if not more, human vascular malformations.
2015-08-19 | GSE72178 | GEO