Coacting enhancers can have complementary functions within gene regulatory networks and promote canalization.,PLOS Genetics

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Coacting enhancers can have complementary functions within gene regulatory networks and promote canalization.
PLOS Genetics ( IF 4.0 ) Pub Date : 2019-12-12 , DOI: 10.1371/journal.pgen.1008525
Leslie Dunipace ₁ , Zsuzsa Ákos ₁ , Angelike Stathopoulos ₁

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Developmental genes are often regulated by multiple enhancers exhibiting similar spatiotemporal outputs, which are generally considered redundantly acting though few have been studied functionally. Using CRISPR-Cas9, we created deletions of two enhancers, brk5' and brk3', that drive similar but not identical expression of the gene brinker (brk) in early Drosophila embryos. Utilizing both in situ hybridization and quantitative mRNA analysis, we investigated the changes in the gene network state caused by the removal of one or both of the early acting enhancers. brk5' deletion generally phenocopied the gene mutant, including expansion of the BMP ligand decapentaplegic (dpp) as well as inducing variability in amnioserosa tissue cell number suggesting a loss of canalization. In contrast, brk3' deletion presented unique phenotypes including dorsal expansion of several ventrally expressed genes and a decrease in amnioserosa cell number. Similarly, deletions were made for two enhancers associated with the gene short-gastrulation (sog), sog.int and sog.dist, demonstrating that they also exhibit distinct patterning phenotypes and affect canalization. In summary, this study shows that similar gene expression driven by coacting enhancers can support distinct, and sometimes complementary, functions within gene regulatory networks and, moreover, that phenotypes associated with individual enhancer deletion mutants can provide insight into new gene functions.

中文翻译：

协同作用增强子可以在基因调节网络内具有互补功能，并促进导管形成。

发育基因通常受到多种增强子的调控，这些增强子表现出相似的时空输出，尽管在功能上很少研究，但通常被认为是多余的。使用CRISPR-Cas9，我们创建了两个增强子brk5'和brk3'的缺失，这些增强子在果蝇早期胚胎中驱动了brink（brk）基因的相似但不相同的表达。利用原位杂交和定量mRNA分析，我们调查了由一种或两种早期作用增强子的去除引起的基因网络状态的变化。brk5'缺失通常会显型化基因突变体，包括BMP配体去Capcappleplegic（dpp）的扩增以及诱导羊膜组织细胞数量的变异，提示失去导管。相反，brk3' 缺失表现出独特的表型，包括几个腹侧表达基因的背侧扩张和羊膜细胞数的减少。同样，缺失了与基因短促性基因（sog）相关的两个增强子，即sog.int和sog.dist，这表明它们也表现出独特的模式表型并影响渠化。总而言之，这项研究表明，由协同增强子驱动的相似基因表达可以支持基因调节网络内独特的，有时是互补的功能，此外，与单个增强子缺失突变体相关的表型可以提供对新基因功能的洞察力。删除了与基因短胃（sog）相关的两个增强子sog.int和sog.dist，这表明它们也表现出独特的模式表型并影响渠化。总而言之，这项研究表明，由协同增强子驱动的相似基因表达可以支持基因调节网络内独特的，有时是互补的功能，此外，与单个增强子缺失突变体相关的表型可以提供对新基因功能的洞察力。删除了与基因短胃（sog）相关的两个增强子sog.int和sog.dist，这表明它们也表现出独特的模式表型并影响渠化。总而言之，这项研究表明，由协同增强子驱动的相似基因表达可以支持基因调节网络内独特的，有时是互补的功能，此外，与单个增强子缺失突变体相关的表型可以提供对新基因功能的洞察力。

更新日期：2019-12-13

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