YY1 Multimerization Peptides for Enhancer-Promoter Loop Disruption
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Solution Overview
Problem
Current understanding of proteins facilitating structural interactions between enhancers and promoters is limited, particularly regarding the mechanisms of enhancer-promoter interactions and their role in gene regulation.
Innovation Solution
The transcription factor YY1 is demonstrated to structure looping interactions between enhancers and promoters through multimerization, and methods are developed to modulate gene expression by manipulating YY1's multimerization, thereby affecting enhancer-promoter DNA loop formation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If transcription factor multimerization is utilized to structure enhancer-promoter loops, then gene expression control is achieved, but the mechanism is poorly understood and difficult to manipulate
Solution Approach 1:
The patent introduces peptides that specifically bind to transcription factor multimers as intermediary molecules. These peptides disrupt the multimerization of transcription factors bound at enhancers and promoters, thereby disrupting enhancer-promoter looping interactions. This intermediary approach provides a controllable mechanism to modulate gene expression by interfering with the protein-protein interactions that structure chromatin loops.
2Adaptability or versatility
If YY1 multimerization is disrupted to modulate gene expression, then enhancer-promoter loop formation is affected, but specificity of target gene identification becomes challenging
Solution Approach 1:
The patent employs peptides with specific binding characteristics that target particular transcription factor multimers at specific genomic locations. By designing peptides that bind to YY1 multimers formed at specific enhancer-promoter interfaces, the method achieves localized disruption of looping interactions. This local quality approach allows selective modulation of specific gene expression programs while maintaining specificity in identifying target enhancer-promoter pairs.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach allows for the modulation of gene expression and treatment of diseases associated with aberrant gene expression, such as cancer, by disrupting or enhancing enhancer-promoter loops dependent on YY1 binding, providing a mechanism to identify target genes and determine enhancer-promoter specificity.
Implementation Method 1
YY1 may structure enhancer-promoter loops by the multimerization (e.g., dimerization) of YY1 molecules bound at two distant DNA elements
Implementation Method 2
transcription factors (TFs) bind these enhancer elements and regulate transcription from the promoters of nearby or distant genes through physical contacts that involve looping of DNA between enhancers and promoters
Implementation Method 3
Transcription factors (TFs) bind these enhancer elements and regulate transcription from the promoters of nearby or distant genes
Data Source
AI summary
The invention relates to methods of modulating the expression of one or more genes in a cell by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops, and thereby modulating the expression of the one or more genes. The invention also relates to treating diseases and conditions involving aberrant gene expression by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops. The invention also relates to methods for screening for compounds that modulate expression of one or more genes in a cell.