Cell-specific and Shared Enhancers Control a High-density Multi-gene Locus Active in Mammary and Salivary Glands

Overview

Journal bioRxiv

Date 2023 Mar 22

PMID 36945503

Authors

Hye Kyung Lee

Michaela Willi

Chengyu Liu

Lothar Hennighausen

Affiliations

Soon will be listed here.

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 a super-enhancer. Five genes are expressed in mammary glands and account for 50% of all mRNAs during lactation, two are salivary-specific and one has dual specificity. We probed the function of eight candidate enhancers through experimental mouse genetics. Deletion of the super-enhancer led to a 98% reduced expression of and in mammary and salivary glands, respectively, and Odam expression was abolished in both tissues. The other three casein genes were only marginally affected. Notably, super-enhancer activity requires the additional presence of a distal -specific enhancer. Our work identifies an evolutionary playground on which regulatory duality of a multigene locus was attained through an ancestral super-enhancer active in mammary and salivary tissue and gene-specific mammary enhancers.

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