Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Genetics. 2021 Mar 3;217(1):1-16. doi: 10.1093/genetics/iyaa028.
To regenerate, damaged tissue must heal the wound, regrow to the proper size, replace the correct cell types, and return to the normal gene-expression program. However, the mechanisms that temporally and spatially control the activation or repression of important genes during regeneration are not fully understood. To determine the role that chromatin modifiers play in regulating gene expression after tissue damage, we induced ablation in Drosophila melanogaster imaginal wing discs, and screened for chromatin regulators that are required for epithelial tissue regeneration. Here, we show that many of these genes are indeed important for promoting or constraining regeneration. Specifically, the two SWI/SNF chromatin-remodeling complexes play distinct roles in regulating different aspects of regeneration. The PBAP complex regulates regenerative growth and developmental timing, and is required for the expression of JNK signaling targets and the growth promoter Myc. By contrast, the BAP complex ensures correct patterning and cell fate by stabilizing the expression of the posterior gene engrailed. Thus, both SWI/SNF complexes are essential for proper gene expression during tissue regeneration, but they play distinct roles in regulating growth and cell fate.
为了再生,受损组织必须愈合伤口,重新生长到适当的大小,替换正确的细胞类型,并恢复正常的基因表达程序。然而,在再生过程中暂时和空间上控制重要基因激活或抑制的机制尚未完全了解。为了确定染色质修饰物在组织损伤后调节基因表达中的作用,我们在果蝇的翅盘上诱导了消融,并筛选了上皮组织再生所需的染色质调节因子。在这里,我们表明,这些基因中的许多基因确实对促进或限制再生很重要。具体来说,这两个 SWI/SNF 染色质重塑复合物在调节再生的不同方面发挥着不同的作用。PBAP 复合物调节再生性生长和发育时间,并且是 JNK 信号靶基因和生长促进因子 Myc 表达所必需的。相比之下,BAP 复合物通过稳定表达后基因 engrailed 来确保正确的模式和细胞命运。因此,两个 SWI/SNF 复合物在组织再生过程中对于适当的基因表达都是必不可少的,但它们在调节生长和细胞命运方面发挥着不同的作用。