ArticleNature communications2023
Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 18 citations in OpenAlex.
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- STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs.Life science alliance · 2025Article
- The Effect of CDKN1A on the Expression of Genes Related to Milk Protein and Milk Fat Synthesis in Bovine Mammary Epithelial Cells.Veterinary sciences · 2025Article
- Disease-Associated Mutations of the STAT5B SH2 Domain Regulate Cytokine-Driven Enhancer Function and Mammary Development.Journal of mammary gland biology and neoplasia · 2025Article
- Data-driven projections of candidate enhancer-activating SNPs in immune regulation.BMC genomics · 2025Article
- Molecular Diversity of the Casein Gene Cluster in Bovidae: Insights from SNP Microarray Analysis.Animals : an open access journal from MDPI · 2024Article
- STAT5B SH2 variants disrupt mammary enhancers and the stability of genetic programs during pregnancy.bioRxiv : the preprint server for biology · 2024Article
- Emergence of saliva protein genes in the secretory calcium-binding phosphoprotein (SCPP) locus and accelerated evolution in primates.bioRxiv : the preprint server for biology · 2024Article
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- Autologous porcine VRAM flap model for VCA research.Frontiers in transplantation · 2024Article
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4 authors at 1 institution in 1 country.
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Abstract
Regulation of high-density loci harboring genes with different cell-specificities remains a puzzle. Here we investigate a locus that evolved through gene duplication and contains eight genes and 20 candidate regulatory elements, including one super-enhancer. Casein genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands, induced 10,000-fold during pregnancy and account for 50% of mRNAs during lactation, Prr27 and Fdcsp are salivary-specific and Odam has dual specificity. We probed the function of 12 candidate regulatory elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, Csn1s2b, Odam and Fdcsp but largely dispensable for Csn1s1, Csn2 and Csn1s2a. Csn3 activation also requires its own local enhancer. Synergism between local enhancers and cytokine-responsive promoter elements facilitates activation of Csn2 during pregnancy. Our work identifies the regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements unique to mammary tissue.
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