In human cells, DNA is packed into chromosomes by wrapping around proteins called histones. Histone proteins contain chains of amino acids called histone tails and can be modified by acetylation. Acetylating histone proteins is important to the cell because it opens up the chromatin and allows for gene expression. Proteins can recognize and bind histone acetylation with a region called a bromodomain. p300 is a bromodomain-containing protein with histone acetyltransferase activity (HAT) which also aids with gene expression and is a coactivator protein of transcription. The bromodomain and HAT domain of this protein is considered the p300 core. Previous research has demonstrated that when fused to a protein called dead Cas9 (dCas9), p300 core has been shown to increase gene expression of neighboring genes. p300 is an important protein to study because mutations within this protein have been observed in cancer cells. The purpose of this research is to determine if cancer mutations impact the coactivator function of p300. It is hypothesized that if these cancer mutations occur in several types of cancers, then it will disrupt the coactivator function of the protein. To test this hypothesis, p300 core mutations will be fused to dCas9 and the expression of neighboring genes will be measured. This research is important because the role of p300 in cancer is not fully understood and this study may provide insight into providing a new way of assessing the effects of p300 cancer mutations.
Myers, Katlyn; Shanle, Erin; and St. John, Meagan, "Determining the effects of cancer mutations on the coactivator function of the p300 core domain in human cells" (2018). Selected Publications. 3.