Zebrafish sin3b mutants are viable but have size, skeletal, and locomotor defects.

Zebrafish sin3b mutants are viable but have size, skeletal, and locomotor defects.
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DOI:
10.1002/dvdy.24581
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发表时间:
2017-11
期刊:
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子:
--
通讯作者:
Sirotkin HI
Sirotkin HI
中科院分区:
其他
文献类型:
--
作者:
Moravec CE;Yousef H;Kinney BA;Salerno-Eichenholz R;Monestime CM;Martin BL;Sirotkin HI

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转录辅抑制子Sin 3从酵母到脊椎动物都高度保守,具有控制细胞命运、细胞周期进程和衰老编程的多种作用。Sin 3蛋白通过与包括Myc、Rest、p53和E2 F在内的转录因子相互作用,将HDAC和其他染色质修饰因子募集到特定位点。大多数脊椎动物都有两个Sin 3家族成员(sin 3a和sin 3b),但斑马鱼有第二个sin 3a家族成员。在小鼠中,sin 3a和sin 3b对胚胎发育至关重要。Sin 3b基因敲除小鼠在生长以及骨和血液分化方面表现出缺陷。为了研究发育过程中对Sin 3b的需求,我们使用CRISPR-Cas9破坏了斑马鱼sin 3b,并研究了对早期发育和运动行为的影响。令人惊讶的是,Sin 3b在斑马鱼中并不是必需的。Sin 3b突变体显示适应性降低、尺寸变小、运动行为改变和骨发育延迟。我们没有检测到Sin 3b在细胞增殖中的作用。我们的sin 3b突变体的分析揭示了更微妙的要求斑马鱼Sin 3b比将预测从其他物种的突变体的分析。
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 HDACs 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.
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