Developmental Biology ( IF 2.5 ) Pub Date : 2020-06-03 , DOI: 10.1016/j.ydbio.2020.05.008 Jeannine M Basta 1 , Ajeet P Singh 2 , Lynn Robbins 3 , Lisa Stout 1 , Michelle Pherson 4 , Michael Rauchman 5
Chromatin-remodeling complexes play critical roles in establishing gene expression patterns in response to developmental signals. How these epigenetic regulators determine the fate of progenitor cells during development of specific organs is not well understood. We found that genetic deletion of Brg1 (Smarca4), the core enzymatic protein in SWI/SNF, in nephron progenitor cells leads to severe renal hypoplasia. Nephron progenitor cells were depleted in Six2-Cre, Brg1flx/flx mice due to reduced cell proliferation. This defect in self-renewal, together with impaired differentiation resulted in a profound nephron deficit in Brg1 mutant kidneys. Sall1, a transcription factor that is required for expansion and maintenance of nephron progenitors, associates with SWI/SNF. Brg1 and Sall1 bind promoters of many progenitor cell genes and regulate expression of key targets that promote their proliferation.
中文翻译:
SWI / SNF核心催化亚基Brg1调节肾单位祖细胞的增殖和分化。
染色质重塑复合体在响应发育信号而建立基因表达模式中起关键作用。这些表观遗传调节剂如何在特定器官发育过程中决定祖细胞的命运尚不清楚。我们发现,肾单位祖细胞中SWI / SNF中核心酶蛋白Brg1(Smarca4)的基因缺失导致严重的肾发育不全。由于减少的细胞增殖,在Six2- Cre,Brg1 flx / flx小鼠中耗尽了肾单位祖细胞。这种自我更新缺陷以及分化受损导致Brg1发生严重的肾单位不足突变肾。Sall1是肾单位祖细胞扩增和维持所必需的转录因子,与SWI / SNF相关。Brg1和Sall1结合许多祖细胞基因的启动子,并调节促进其增殖的关键靶标的表达。