The impact of the destabilization of the STAT3 and S100A8/9 complex on the DNA-binding capacity of STAT3

To assess the effect of STAT3's interaction with S100A8/9 on its DNA affinity within the mouse colorectal cancer cell line MC38, we engineered both wild-type cells and cells harboring deletion mutations at the complex binding sites. We utilized Cleavage Under Targets and Tagmentation (CUT&Tag) technology to compare the DNA binding peaks of STAT3 before and after these mutations. The regulatory role of the complex on STAT3, functioning as either a transcription factor or coactivator, was elucidated by analyzing parameters such as peak signal intensity and genomic distribution. Additionally, to ascertain whether STAT3 interacted with S100A8 or S100A9 on DNA, we evaluated the distribution and overlap of CUT&Tag signal peaks for STAT3, S100A8, and S100A9 in wild-type MC38 cells. This analysis aimed to determine the involvement of the STAT3/S100A8/9 complex in modulating STAT3's binding to the promoters or enhancers of target genes.