Moravec Cara E, Yousef Hakeem, Kinney Brian A, Salerno-Eichenholz Ryan, Monestime Camillia M, Martin Benjamin L, Sirotkin Howard I
Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, New York.
Genetics Gradate Program Stony Brook University, Stony Brook, New York.
Dev Dyn. 2017 Nov;246(11):946-955. doi: 10.1002/dvdy.24581. Epub 2017 Sep 25.
The transcriptional co-repressor Sin3 is highly conserved from yeast to vertebrates and has multiple roles controlling cell fate, cell cycle progression, and senescence programming. Sin3 proteins recruit histone deacetylases and other chromatin modifying factors to specific loci through interactions with transcription factors including Myc, Rest, p53 and E2F. Most vertebrates have two Sin3 family members (sin3a and sin3b), but zebrafish have a second sin3a paralogue. In mice, sin3a and sin3b are essential for embryonic development. Sin3b knockout mice show defects in growth as well as bone and blood differentiation.
To study the requirement for Sin3b during development, we disrupted zebrafish sin3b using CRISPR-Cas9, and studied the effects on early development and locomotor behavior.
Surprisingly, Sin3b is not essential in zebrafish. sin3b mutants show a decrease in fitness, small size, changes to locomotor behavior, and delayed bone development. We did not detect a role for Sin3b in cell proliferation. Our analysis of the sin3b mutant revealed a more nuanced requirement for zebrafish Sin3b than would be predicted from analysis of mutants in other species. Developmental Dynamics 246:946-955, 2017. © 2017 Wiley Periodicals, Inc.
转录共抑制因子Sin3从酵母到脊椎动物高度保守，在控制细胞命运、细胞周期进程和衰老编程方面具有多种作用。Sin3蛋白通过与包括Myc、Rest、p53和E2F在内的转录因子相互作用，将组蛋白脱乙酰酶和其他染色质修饰因子招募到特定基因座。大多数脊椎动物有两个Sin3家族成员（sin3a和sin3b），但斑马鱼有第二个sin3a旁系同源物。在小鼠中，sin3a和sin3b对胚胎发育至关重要。Sin3b基因敲除小鼠表现出生长以及骨骼和血液分化方面的缺陷。
为了研究发育过程中对Sin3b的需求，我们使用CRISPR-Cas9技术破坏了斑马鱼的sin3b，并研究了其对早期发育和运动行为的影响。
令人惊讶的是，Sin3b在斑马鱼中并非必不可少。sin3b突变体表现出适应性下降、体型变小、运动行为改变以及骨骼发育延迟。我们未检测到Sin3b在细胞增殖中的作用。我们对sin3b突变体的分析揭示，斑马鱼Sin3b的需求比从其他物种突变体分析中预测的更为细微。《发育动力学》246:946 - 955, 2017年。© 2017威利期刊公司。
