The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis.
The zebrafish moonshine gene encodes transcriptional intermediary factor 1gamma, an essential regulator of hematopoiesis.
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DOI：
10.1371/journal.pbio.0020237
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发表时间：
2004-08
期刊：
影响因子：
9.8
通讯作者：
Zon LI
中科院分区：
文献类型：
--
作者：
Ransom DG;Bahary N;Niss K;Traver D;Burns C;Trede NS;Paffett-Lugassy N;Saganic WJ;Lim CA;Hersey C;Zhou Y;Barut BA;Lin S;Kingsley PD;Palis J;Orkin SH;Zon LI
造血是由血统特异的DNA结合蛋白精确协调的，这些蛋白与辅助激活因子和辅助抑制因子共同调节转录。斑马鱼月光(MON)基因的突变特别破坏了胚胎和成人的造血，导致严重的红细胞再生障碍。我们报道了MON编码哺乳动物转录中介因子1γ(TIF1γ)(或TRIM33)的同源基因，TIF1是辅助激活因子和辅助抑制因子家族中的一个成员。在发育过程中，MON突变体的造血祖细胞不能表达正常水平的造血转录因子，包括GATA1，并经历凋亡。三种不同的MON突变等位基因都编码过早终止密码子，野生型tif1γ的强制表达挽救了纯合MON突变的胚胎造血。令人惊讶的是，在γ表达之前，合子TIF1GATA1mRNA的高水平表达描绘了在造血干细胞和祖细胞形成过程中的腹侧中胚层。移植研究表明，TIF1γ在红系前体细胞分化过程中以细胞自主的方式发挥作用。对小鼠红系细胞株的研究表明，Tif1γ蛋白定位于新的核灶中，并且在红系细胞成熟过程中表达减少。我们的结果确立了这种转录中介因子在脊椎动物造血细胞分化中的主要作用。通过对斑马鱼的遗传分析，发现了一种在红细胞发育早期起作用的新基因。该基因编码一个众所周知的转录因子家族的成员。
Hematopoiesis is precisely orchestrated by lineage-specific DNA-binding proteins that regulate transcription in concert with coactivators and corepressors. Mutations in the zebrafish moonshine (mon) gene specifically disrupt both embryonic and adult hematopoiesis, resulting in severe red blood cell aplasia. We report that mon encodes the zebrafish ortholog of mammalian transcriptional intermediary factor 1γ (TIF1γ) (or TRIM33), a member of the TIF1 family of coactivators and corepressors. During development, hematopoietic progenitor cells in mon mutants fail to express normal levels of hematopoietic transcription factors, including gata1, and undergo apoptosis. Three different mon mutant alleles each encode premature stop codons, and enforced expression of wild-type tif1γ mRNA rescues embryonic hematopoiesis in homozygous mon mutants. Surprisingly, a high level of zygotic tif1γ mRNA expression delineates ventral mesoderm during hematopoietic stem cell and progenitor formation prior to gata1 expression. Transplantation studies reveal that tif1γ functions in a cell-autonomous manner during the differentiation of erythroid precursors. Studies in murine erythroid cell lines demonstrate that Tif1γ protein is localized within novel nuclear foci, and expression decreases during erythroid cell maturation. Our results establish a major role for this transcriptional intermediary factor in the differentiation of hematopoietic cells in vertebrates. A new gene acting early in red blood cell development is discovered by genetic analysis in zebrafish. The gene encodes a member of a well-known family of transcription factors
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影响因子：
30.8
作者：
Brownlie, A;Donovan, A;Zon, LI
通讯作者：
Zon, LI
影响因子：
5.6
作者：
Peng, HZ;Feldman, I;Rauscher, FJ
通讯作者：
Rauscher, FJ
DOI：
10.1073/pnas.041616998
发表时间：
2001-02-13
影响因子：
11.1
作者：
Abrink, M;Ortiz, JA;Losson, R
通讯作者：
Losson, R
影响因子：
10.5
作者：
Friedman, JR;Fredericks, WJ;Rauscher, FJ
通讯作者：
Rauscher, FJ
DOI：
10.1073/pnas.082695299
发表时间：
2002-04-16
影响因子：
11.1
作者：
Lyons, SE;Lawson, ND;Liu, PP
通讯作者：
Liu, PP