Transcriptional regulation governs lineage specification in all tissues including the mammary gland, yet our understanding of the mechanisms controlling this remains limited. Enhancers and promoters are cis-regulatory elements of the genome that are critical for transcriptional regulation and cell differentiation.  Understanding the gene regulation of lineage specification is vital, development of breast cancer subtypes occurs through alterations in different cells along the differentiation hierarchy. Transcription factors (TF) are proteins that coordinate lineage specificity. We hypothesise that cis-regulatory elements of lineage specific TFs are critical to the differentiation of the two epithelial lineages of the mammary gland. We utilised CRISPR-activation (CRISPRa) to interrogate the role of lineage specific TFs in mammary linage specification through two strategies. Our first strategy was to use CRISPRa to target putative enhancer elements of lineage TFs to interrogate the effects of this on target gene expression. Putative enhancer regions were identified from previous Omni-C analysis of primary murine mammary cell subpopulations. Multiple guides covering several putative enhancer regions were transduced into a murine normal-like mammary epithelial cell line expressing CRISPRa. A proportion of guides targeting putative enhancers of ΔNp63, Snai2, Msx2, Elf5 and Gata3 TFs increased target gene expression compared to a non-targeting control guide, providing evidence that these putative locations were true enhancers. While increased expression of these TFs was achieved through enhancer targeting, limited changes in downstream lineage specific genes were detected by RNA-seq in this cell line model. Our second strategy is to utilise the CRISPRa mouse to investigate if activation of lineage-specific TF expression can shift cellular lineage. Preliminary data suggest that activating expression of luminal TFs in basal cells through CRISPRa-targeting of endogenous promoters leads to emergence of luminal lineage characteristics in a subset of transduced basal cells.