GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296152/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296152GEOGSEfalseSustained MYB activity drives emergent enhancer activation and precise enhancer-promoter interactions [ATAC-seq]Transcription factors (TFs) are key effectors of enhancer activity. MYB is a critical hematopoietic TF that is frequently dysregulated in cancer. Despite its well-established role, the exact mechanisms by which MYB influences enhancer function—and the specific stages of enhancer activation at which it operates—remain poorly understood. Using high resolution Micro-Capture-C, we show that upon MYB degradation, highly defined enhancer-promoter interactions at specific MYB binding sites are lost. Loss of these interactions, together with other hallmarks of enhancer activity—reduced H3 lysine-27 acetylation and enhancer RNA transcription—correlates with significant downregulation of target gene expression in leukemia, indicating that MYB mediates transcription activation via maintenance of enhancer function. When anchored to DNA within a gene desert region that is devoid of histone marks and active transcription, the MYB transactivation domain is sufficient and necessary for the nucleation of an enhancer-like region. This results in the activation of transcription from distal cryptic elements and the establishment of long-range chromatin interactions up to 400 kb away from the anchor point. Together, these results indicate that MYB activity alone is sufficient to induce long-range interactions and transcription, achieving this through highly precise enhancer-promoter crosstalk.2026/05/01GSE296152GSM8965989GSM8965988GSM8965990GSM8965994GSM8965993GSM8965992GSM8965991GSM8965987GSM896598619057296152Mus musculus