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Status |
Public on Jul 28, 2023 |
Title |
Cell-specific and shared regulatory elements control a multi-gene locus active in mammary and salivary glands [Bisulfite-seq] |
Organism |
Mus musculus |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
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. Five genes (Csn1s1, Csn2, Csn1s2a, Csn1s2b, Csn3) are expressed in mammary glands and account for 50% of mRNAs during lactation, two (Prr27, Fdcsp) are salivary-specific and one (Odam) has dual specificity. We probed the function of 12 candidate control elements, individually and in combination, in the mouse genome. The super-enhancer is essential for the expression of Csn3, 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 facilitated the 10,000-fold activation of Csn2 during pregnancy. Our work identifies regulatory complexity of a multigene locus with an ancestral super-enhancer active in mammary and salivary tissue and local enhancers and promoter elements.
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Overall design |
Bisulfite-seq in WT lactating mammary tissues and liver tissues
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Contributor(s) |
Lee HK |
Citation(s) |
37591874, 40163145 |
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Submission date |
May 01, 2023 |
Last update date |
Apr 10, 2025 |
Contact name |
Hye Kyung Lee |
E-mail(s) |
hyekyung.lee@nih.gov
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Phone |
301-435-6635
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Organization name |
National Institutes of Health (NIH)
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Department |
National Institute of Diabetes and Digestive and Kidney (NIDDK)
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Lab |
Laboratory of Genetics and Physiology
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Street address |
8 CENTER DR RM 107
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City |
Bethesda |
State/province |
MD |
ZIP/Postal code |
20892 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (5)
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This SubSeries is part of SuperSeries: |
GSE231441 |
Cell-specific and shared regulatory elements control a multi-gene locus active in mammary and salivary glands |
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Relations |
BioProject |
PRJNA965829 |