Mesh : Animals Cell Differentiation / genetics DNA-Binding Proteins / deficiency genetics physiology Embryonic and Fetal Development / genetics Fungal Proteins / genetics physiology Gene Deletion Gene Expression Regulation, Developmental Gene Targeting Genes, Lethal Genotype Hematopoiesis / genetics Mice Mice, Inbred C57BL Mice, Knockout / embryology genetics Models, Animal Multigene Family Neovascularization, Physiologic / genetics Protein Structure, Tertiary Proto-Oncogene Protein c-ets-1 Proto-Oncogene Protein c-ets-2 Proto-Oncogene Protein c-fli-1 Proto-Oncogene Proteins / deficiency genetics physiology Proto-Oncogene Proteins c-ets Radiation Chimera Repressor Proteins Trans-Activators / deficiency genetics physiology Transcription Factors / deficiency genetics physiology

来  源:   DOI:10.1038/sj.onc.1204038   PDF(Sci-hub)

Abstract:
The Ets family of transcription factors is one of a growing number of master regulators of development. This family was originally defined by the presence of a conserved DNA binding domain, the Ets domain. To date, nearly 30 members of this family have been identified and implicated in a wide range of physiological and pathological processes. Despite the likely importance of Ets-family members, each of their precise roles has not been delineated. Herein, we describe the elucidation of essential functions of a few of these family members in vivo using knockout mouse models. Of the knockouts generated to date, the majority shows important functions in hematopoiesis, ranging from PU.1, a principle regulator of myelo-lymphopoiesis, to Spi-B which regulates the proper function of terminally differentiated cells. Ets1 was shown to be of intermediate importance as a regulator of pan-lymphoid development. Other Ets family members such as Fli1 and TEL1 display distinct and/or overlapping functions in vasculo/angiogenesis, hemostasis and hematopoiesis. The remaining knockouts generated, Ets2 and Er81, show non-hematopoietic defects related to extraembryonic development and neurogenesis, respectively. The pioneering group of knockout models described reveals only the most distinct functions of each of these Ets family members. A better understanding of the roles and hierarchies of Ets family members in cellular differentiation will come with the generation of new null alleles in previously untargeted family members, more mutant alleles in members already disrupted, double knockouts, ES cell differentiation and chimera rescue experiments, and tissue-specific inducible knockouts.
摘要:
Ets转录因子家族是越来越多的发育主要调控因子之一。这个家族最初是由保守的DNA结合域的存在定义的,Ets域。迄今为止,该家族的近30个成员已被鉴定并参与了广泛的生理和病理过程。尽管埃茨家族成员可能很重要,他们每个人的确切角色都没有被划定。在这里,我们描述了使用基因敲除小鼠模型在体内阐明其中一些家族成员的基本功能。在迄今为止产生的淘汰赛中,大多数在造血中表现出重要的功能,从PU.1开始,骨髓淋巴细胞生成的主要调节因子,调节终末分化细胞的正常功能的Spi-B。Ets1作为泛淋巴发育的调节剂被证明具有中等重要性。其他Ets家族成员如Fli1和TEL1在血管/血管生成中表现出不同和/或重叠的功能,止血和造血。剩下的淘汰赛产生了,Ets2和Er81显示与胚胎外发育和神经发生相关的非造血缺陷,分别。所描述的淘汰赛模型的开创性小组仅揭示了这些Ets家族成员中每个成员的最独特功能。更好地了解Ets家族成员在细胞分化中的作用和层次结构将伴随着在以前未靶向的家族成员中产生新的无效等位基因,已经破坏的成员中有更多的突变等位基因,双淘汰赛,ES细胞分化和嵌合体拯救实验,和组织特异性诱导型敲除。
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