Unexpected Gene Expression ‘Spatial Grammar’ Discovered

• Researchers Sascha Duttke and his team have discovered a new gene expression’spatial grammar’.
• The human genome, which contains information about development, functioning, growth, and reproduction, takes up only about 2 MB of space.
• Transcription factors, proteins that bind to specific portions of the DNA, control the rate at which the cell transcribes genetic information from DNA to RNA.
• The fate of a gene being transcribed depends on the location of the transcription factor binding site relative to the location where transcription begins.
• The findings can help refine genomic tools and algorithms that predict gene expression, which can inform new diagnostic and therapeutic strategies for diseases like cancers caused by mutations in regulatory elements.
• The researchers found that the binding sites for activator transcription factor NRF1 were located before the start sites and for factor YY1 it was located after the start site.
• The relative position of the start site affected how the transcription factor behaved.
• The researchers also synthetically inserted binding sites for six factors at different distances from the start sites in some DNA sequences.
• The researchers studied the relevance of these effects in human diseases and observed position-dependent effects of disease-associated variants based on the location of the start sites and the binding sites.
• The findings have “vast potential applications,” including helping researchers identify and predict disease-associated mutations, called polymorphisms, that occur outside genes and provide a basis for therapeutic interventions.
• The study adds crucial new insights about how positioning and spacing relative to start sites can impact the ability of factors to either activate or repress gene expression.