4See: A Flexible Browser to Explore 4C Data

It is established that transcription of many metazoan genes is regulated by distal regulatory sequences beyond the promoter. Enhancers have been identified at up to megabase distances from their regulated genes, and/or proximal to or within the introns of unregulated genes. The unambiguous identification of the target genes of newly identified regulatory elements can thus be challenging. Well-studied enhancers have been found to come into direct physical proximity with regulated genes, presumably by the formation of chromatin loops. Chromosome conformation capture (3C) derivatives that assess the frequency of proximity between different genetic elements is thus a popular method for exploring gene regulation by distal regulatory elements. For studies of chromatin loops and promoter-enhancer communication, 4C (circular chromosome conformation capture) is one of the methods of choice, optimizing cost (required sequencing depth), throughput, and resolution. For ease of visual inspection of 4C data we present 4See, a versatile and user-friendly browser. 4See allows 4C profiles from the same bait to be flexibly plotted together, allowing biological replicates to either be compared, or pooled for comparisons between different cell types or experimental conditions. 4C profiles can be integrated with gene tracks, linear epigenomic profiles, and annotated regions of interest, such as called significant interactions, allowing rapid data exploration with limited computational resources or bioinformatics expertise

Timing of first shoot topping and its impact on grapevine canopy and cluster morphology as well as on susceptibility to bunch rot.

info:eu-repo/semantics/publishe

Context-dependent transcriptional remodeling of TADs during differentiation

Metazoan chromosomes are organized into discrete domains (TADs), believed to contribute to the regulation of transcriptional programs. Despite extensive correlation between TAD organization and gene activity, a direct mechanistic link is unclear, with perturbation studies often showing little effect. To follow TAD dynamics during development, we used Capture Hi-C to interrogate the TADs around key differentially expressed genes during mouse thymocyte maturation, uncovering specific remodeling events. Notably, one TAD boundary was broadened to accommodate RNA polymerase elongation past the border, and sub-domains were formed around some activated genes without changes in CTCF binding. The ectopic induction of one gene was sufficient to recapitulate microdomain formation in embryonic stem cells, providing strong evidence that transcription can directly remodel chromatin

Transcription induces context-dependent remodeling of chromatin architecture during differentiation.

Metazoan chromosomes are organized into discrete spatial domains (TADs), believed to contribute to the regulation of transcriptional programs. Despite extensive correlation between domain organization and gene activity, a direct mechanistic link is unclear, with perturbation studies often showing little effect. To follow chromatin architecture changes during development, we used Capture Hi-C to interrogate the domains around key differentially expressed genes during mouse thymocyte maturation, uncovering specific remodeling events. Notably, one TAD boundary was broadened to accommodate RNA polymerase elongation past the border, and subdomains were formed around some activated genes without changes in CTCF binding. The ectopic induction of some genes was sufficient to recapitulate domain formation in embryonic stem cells, providing strong evidence that transcription can directly remodel chromatin structure. These results suggest that transcriptional processes drive complex chromosome folding patterns that can be important in certain genomic contexts

Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene

International audienceThe Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/ Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-through-put enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus