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Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands
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Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands
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Journal Article
Cell-specific and shared regulatory elements control a multigene locus active in mammary and salivary glands
2023
Overview
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.
The authors investigate the regulatory complexity of a multigene locus with 20 candidate regulatory elements, including an ancestral super-enhancer, active in mammary and salivary tissue and local enhancers and promoter elements unique to mammary tissue.
