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12/6/2020

3-D shape of human genome essential for robust inflammatory response

3-D shape of human genome essential for robust inflammatory response


News from CRG


The three-dimensional structure of the human genome is essential for providing a rapid and robust inflammatory response but is surprisingly not vital for reprogramming one cell type into another, according to research published today in Nature Genetics. The findings shed new light on the fundamental relationship between how a genome folds and the function of a cell.

Each human cell has two metres of genome condensed down into 10 microns within the nucleus. Folding the genome is more than a packaging solution, it helps genes make physical contact with other genes or a regulatory element that may be located quite a distance away along the chromosome. This is crucial for cell function.

The precise 3D structure of the genome is weaved together by architectural proteins. CTCF is one of the most prominent of these structural proteins. Collectively, it helps to shape the overall three-dimensional structure of the genome, which is why CTCF has been shown to be essential for embryonic development, DNA repair and cell cycles, as well as many other vital processes that make it an intensive area of research.ç

CTCF's role in transdifferentiation is particularly controversial. This is when a cell reprograms itself into another type of cell without undergoing an intermediate state, such as pancreatic alpha cells turning into insulin-secreting beta cells after injury of the pancreas.

To study this, researchers at the Centre for Genomic Regulation (CRG) developed a unique system where human B cells can be induced into becoming macrophages. To uncover CTCF's role in this process they used CRISPR genome editing tools to degrade the protein and study changes in genome organisation as the cell fate changes.

 

More information:
CRG website