GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296154/primaryOK200OtherMus musculusOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296154GEOGSEfalseSustained MYB activity drives emergent enhancer activation and precise enhancer-promoter interactions [Capture-C]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.2026/05/01GSE296154GSM8966039GSM8966035GSM8966036GSM8966037GSM8966038GSM8966053GSM8966031GSM8966032GSM8966033GSM8966034GSM8966050GSM8966051GSM8966030GSM8966052GSM8966028GSM8966029GSM8966024GSM8966046GSM8966047GSM8966025GSM8966048GSM8966026GSM8966027GSM8966049GSM8966042GSM8966021GSM8966043GSM8966044GSM8966022GSM8966045GSM8966023GSM8966040GSM89660411905716417296154Mus musculus