DNA organization within cells is a complex and sophisticated process. This high level of complexity is due to the hundreds of thousands of interactions that can be enabled through organization. It is a known that promoter elements and enhancer elements work in unison to regulate gene expression. Often times enhancers are found hundreds of kilo-bases away from their interacting promoter elements. These enhancers initiate promoter activation via interactions amongst transcription factor binding sites. As previously mentioned, sometimes the enhancers are located many kilo-bases away from their promoter, so how can they interact? Chromosome looping is one way for cells to participate in long-range interactions, such as the enhancer-promoter
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Loop formation occurs at high frequency and with such speed that they are hard to analyze. However, in Drosophila, there have been transcription factors that are known to be associated with chromatin looping. The GAGA transcription factor in drosophila initiates gene expression. GAGA factors bind to sequences that are rich in GA/CT sequences where they alter the conformation of the chromatin, allowing the DNA to be accessed by transcriptional factors. GAG is also one of the factors known to associate with chromatin looping. GAGA is known to influence promoter activation via an enhancer that is localized to another DNA molecule[2]. GAGA has a specialized ability to bind to two DNA molecules at the same time, making the promoter-enhancer interaction possible. The GAGA factor acts a bridge between the promoter and enhancer elements. [1]
In order for chromatin looping to occur, the chromatin fiber must be extremely flexible and able to adapt to different configurations based on environmental and cellular cues. The fiber flexibility is mediated by histone modifications[3]. The CCCTC-binding factor (CTCF) is a protein that is involved in both long-range looping interactions and histone modifications. The initial discovery of CTCF
Loop formation occurs at high frequency and with such speed that they are hard to analyze. However, in Drosophila, there have been transcription factors that are known to be associated with chromatin looping. The GAGA transcription factor in drosophila initiates gene expression. GAGA factors bind to sequences that are rich in GA/CT sequences where they alter the conformation of the chromatin, allowing the DNA to be accessed by transcriptional factors. GAG is also one of the factors known to associate with chromatin looping. GAGA is known to influence promoter activation via an enhancer that is localized to another DNA molecule[2]. GAGA has a specialized ability to bind to two DNA molecules at the same time, making the promoter-enhancer interaction possible. The GAGA factor acts a bridge between the promoter and enhancer elements. [1]
In order for chromatin looping to occur, the chromatin fiber must be extremely flexible and able to adapt to different configurations based on environmental and cellular cues. The fiber flexibility is mediated by histone modifications[3]. The CCCTC-binding factor (CTCF) is a protein that is involved in both long-range looping interactions and histone modifications. The initial discovery of CTCF