An autoregulatory enhancer controls mammary-specific STAT5 functions
Transcriptomics Dataset
FAIR Metrics
0 evaluations
General Information
| Accession | GSE72724 |
| Title | An autoregulatory enhancer controls mammary-specific STAT5 functions |
| Description | Signal Transducers and Activators of Transcription (STATs) are principal transcription factors downstream of cytokine receptors. Although STAT5A is expressed in most tissues it remains to be understood why its premier, non-redundant functions are restricted to prolactin-induced mammary gland development. We report that the ubiquitously expressed Stat5a/b locus is subject to lineage-specific transcriptional control in mammary epithelium. Genome-wide surveys of epigenetic status and transcription factor occupancy uncovered a putative mammary-specific enhancer within the intergenic sequences separating the two Stat5 genes. This region exhibited several hallmarks of genomic enhancers, including DNaseI hypersensitive sites, H3K27 acetylation and binding by GR and MED1. Mammary-specific STAT5 binding was obtained at two canonical STAT5 binding motifs. CRISPR/Cas9-mediated genome editing was used to delete these STAT5 binding sites in mice and determine their biological function. Mutant animals exhibited an 80%% reduction of Stat5 levels in mammary epithelium and a concomitant reduction of STAT5-dependent gene expression. Transcriptome analysis identified a class of mammary-restricted genes that was particularly dependent on high STAT5 levels as a result of the intergenic enhancer. Taken together, the mammary-specific enhancer enables a positive feedback circuit that underlies the remarkable abundance of STAT5 and, in turn, controls the efficacy of STAT5-dependent mammary physiology. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72724 |
| Repository | Gene Expression Omnibus |
Related Datasets
GSE37646
Distinct STAT5 concentrations uniquely control establishment and differentiation of mammary epithelium during pregnancy
1
GSE42878
Pregnancy-induced gene expression and differentiation of mouse mammary epithelium are co-governed by Nuclear Factor IB (NFIB) and STAT5
1
GSE65621
Asymmetry of STAT action in driving IL-27 and IL-6 transcriptional outputs and cytokine specificity
3
GSE48970
Contribution of the STAT1alpha and STAT1beta isoforms to IFN-gamma mediated innate immunity
21
Tools
used to analyze the dataset
Canned Analyses
generated with the dataset
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.
