ArticleNature communications2021
Redundant and non-redundant cytokine-activated enhancers control Csn1s2b expression in the lactating mouse mammary gland.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- H3K4me3 CUT&Tag and Transcriptome Analysis Reveal the Epigenetic Regulatory Landscape in Mammary Gland Tissues of Yili Horses at Different Lactation Stages.Animals : an open access journal from MDPI · 2026Article
- STAT5B leukemic mutations, altering SH2 tyrosine 665, have opposing impacts on immune gene programs.Life science alliance · 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
- STAT5B SH2 variants disrupt mammary enhancers and the stability of genetic programs during pregnancy.bioRxiv : the preprint server for biology · 2024Article
- Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands.Nature communications · 2023Article
- 3D genomics and its applications in precision medicine.Cellular & molecular biology letters · 2023Article
- Cell-specific and shared enhancers control a high-density multi-gene locus active in mammary and salivary glands.bioRxiv : the preprint server for biology · 2023Article
- Cell-specific and shared enhancers control a high-density multi-gene locus active in mammary and salivary glands.Research square · 2023Article
- TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors.GigaScience · 2022Article
- Evaluation of the α-casein (CSN1S1) locus as a potential target for a site-specific transgene integration.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Enhancers are transcription factor platforms that synergize with promoters to control gene expression. Here, we investigate enhancers that activate gene expression several hundred-fold exclusively in the lactating mouse mammary gland. Using ChIP-seq for activating histone marks and transcription factors, we identify two candidate enhancers and one super-enhancer in the Csn1s2b locus. Through experimental mouse genetics, we dissect the lactation-specific distal enhancer bound by the mammary-enriched transcription factors STAT5 and NFIB and the glucocorticoid receptor. While deletions of canonical binding motifs for NFIB and STAT5, individually or combined, have a limited biological impact, a non-canonical STAT5 site is essential for enhancer activity during lactation. In contrast, the intronic enhancer contributes to gene expression only in late pregnancy and early lactation, possibly by interacting with the distal enhancer. A downstream super-enhancer, which physically interacts with the distal enhancer, is required for the functional establishment of the Csn1s2b promoter and gene activation. Lastly, NFIB binding in the promoter region fine-tunes Csn1s2b expression. Our study provides comprehensive insight into the anatomy and biology of regulatory elements that employ the JAK/STAT signaling pathway and preferentially activate gene expression during lactation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.