Hospital del Mar Research Institute Hospital del Mar Research Institute



3D genome organization and cell fate determination

Virtual, a les 12:00h

Us convidem al pròxim IMIM Invited speakers Seminar, que tindrà lloc el dijous 17/02/2022 a les 12:00 h. El títol serà "3D genome organization and cell fate determination", a càrrec del Dr. Gregoire Stik. Hematopoietic stem cells, transdifferentiation & reprogramming laboratory. Centre for Genomic Regulation (CRG).


We invite you to the next IMIM Invited speakers Seminar, which will take place on Thursday 17/02/2022 at 12:00 h. The title will be "3D genome organization and cell fate determination",by Dr. Gregoire Stik. Hematopoietic stem cells, transdifferentiation & reprogramming laboratory. Centre for Genomic Regulation (CRG).


The fine regulation of gene expression is crucial to guarantee tissue homeostasis and its alteration drives cell disorders and diseases. In the nucleus, the 3D chromatin organization has emerged as a key feature for the proper regulation of gene expression. Chromosome conformation capture technique and its derivatives such as Hi-C enabled the mapping of DNA interactions and revealed a precise and hierarchical folding of the chromatin. In mammals, CTCF and the cohesin complex create submegabase structures with elevated internal chromatin contact frequencies, called topologically associating domains (TADs). Although TADs can contribute to transcriptional regulation, ablation of TAD organization by disrupting CTCF or the cohesin complex causes modest gene expression changes. In contrast, CTCF is required for cell cycle regulation, embryonic development and formation of various adult cell types. To uncouple the role of CTCF in cell-state transitions and cell proliferation, we studied the effect of CTCF depletion during the conversion of human B cells into macrophages with minimal cell division. CTCF depletion disrupts TAD organization but not cell transdifferentiation. In contrast, CTCF depletion in induced macrophages impairs the full-blown upregulation of inflammatory genes after exposure to endotoxin. Our results demonstrate that CTCF-dependent genome topology is not strictly required for a functional cell-fate conversion but facilitates a rapid and efficient response to an external stimulus.


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