细胞特异性和共享增强子控制着一个在乳腺和唾液腺中活跃的高密度多基因位点。
Cell-specific and shared enhancers control a high-density multi-gene locus active in mammary and salivary glands.
作者信息
Lee Hye Kyung, Willi Michaela, Liu Chengyu, Hennighausen Lothar
机构信息
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland 20892, USA.
Transgenic Core, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA.
出版信息
bioRxiv. 2023 Feb 7:2023.02.06.527373. doi: 10.1101/2023.02.06.527373.
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.
含有具有不同细胞特异性基因的高密度基因座的调控仍然是一个谜。在这里，我们研究了一个通过基因复制进化而来的基因座，它包含八个基因和20个候选调控元件，其中包括一个超级增强子。五个基因在乳腺中表达，在哺乳期占所有mRNA的50%，两个基因是唾液特异性的，一个具有双重特异性。我们通过实验小鼠遗传学探究了八个候选增强子的功能。超级增强子的缺失分别导致乳腺和唾液腺中 和 的表达降低98%，并且在两种组织中Odam的表达均被消除。其他三个酪蛋白基因仅受到轻微影响。值得注意的是，超级增强子的活性需要额外存在一个远端 特异性增强子。我们的工作确定了一个进化场所，在这个场所中，一个多基因座的调控二元性是通过在乳腺和唾液组织中活跃的祖先超级增强子以及基因特异性乳腺增强子实现的。
Zotero 插件