Function of PU.1 (Spi-1), C/EBP, and AML1 in early myelopoiesis: regulation of multiple myeloid CSF receptor promoters.
Function of PU.1 (Spi-1), C/EBP, and AML1 in early myelopoiesis: regulation of multiple myeloid CSF receptor promoters.
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PU.1 (Spi-1)、C/EBP 和 AML1 在早期骨髓生成中的功能：多髓系 CSF 受体启动子的调节。
DOI：
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发表时间：
1996
影响因子：
--
通讯作者：
D. G. Tenen
中科院分区：
文献类型：
--
作者：
Dong;S. Hohaus;M. Voso;Hui;L. Smith;C. Hetherington;D. G. Tenen
我们对细胞系中髓样CSF受体（M、GM和G）启动子的研究发现，启动子很小，并且都被PU.1和C/EBP蛋白激活。迄今为止，我们只发现了C/EBP alpha参与的证据，尽管需要进一步的实验来排除C/EBP beta和C/EBP delta在受体基因表达中的作用。这些研究提出了一种造血模型（图2），其中多能细胞的谱系定型决定是由某些转录因子的替代表达模式做出的，这些转录因子随后激活生长因子受体，使这些细胞对适当的生长因子做出反应，从而增殖和存活。例如，加塔-1的表达激活其自身的表达以及促红细胞生成素受体的表达，诱导这些细胞能够对促红细胞生成素应答。类似地，PU.1的表达激活其自身的启动子，并开启三种髓样CSF受体（M、GM和G），推动这些细胞沿着髓样分化的途径。C/EBP蛋白，特别是C/EBP α，对于髓样受体启动子功能也是至关重要的，并且也可以通过自身调节机制起作用。小鼠C/EBP α在其自身的启动子中具有C/EBP结合位点。人C/EBP α通过激活USF转录因子自动调节其自身在脂肪细胞中的表达。在分化过程中后期表达的髓样基因，如CD 11b，也被PU.1激活，PU.1在成熟髓样细胞中表达水平最高，但不被C/EBP α激活，C/EBP α在分化的鼠髓样细胞系中下调。与该模型一致的发现是，红系细胞中PU. 1的过表达阻断红系分化，导致红白血病，并且髓系中加塔-1的过表达阻断髓系分化。虽然这些发现为理解骨髓基因调控提供了一些框架，但在不久的将来还有许多关键问题需要解决：在人类CD 34+细胞的骨髓分化和激活过程中，C/EBP蛋白的表达模式是什么？C/EBP和AML 1蛋白的靶向破坏和其他突变对骨髓发育和受体表达有什么影响？这三种不同类型的因子（ets、碱性区域拉链和Runt结构域蛋白）之间的相互作用是什么？这些因子的易位、突变和表达改变的影响是什么，特别是在不同形式的AML中？
Our studies of the promoters of the myeloid CSF receptors (M, GM, and G) in cell lines have led to the findings that the promoters are small, and are all activated by the PU.1 and C/EBP proteins. To date, we have only found evidence for involvement of C/EBP alpha, although further experiments will be needed to exclude the role of C/EBP beta and C/EBP delta in receptor gene expression. These studies suggest a model of hematopoiesis (Fig. 2) in which the lineage commitment decisions of multipotential cells are made by the alternative patterns of expression of certain transcription factors, which then activate growth factor receptors which allow those cells to respond to the appropriate growth factor to proliferate and survive. For example, expression of GATA-1 activates its own expression, as well as that of the erythropoietin receptor, inducing these cells to be capable of responding to erythropoietin. Similarly, expression of PU.1 activates its own promoter, and turns on the three myeloid CSF receptors (M, GM, and G), pushing these cells along the pathway of myeloid differentiation. C/EBP proteins, particularly C/EBP alpha, are also critical for myeloid receptor promoter function, and may also act via autoregulatory mechanisms. Murine C/EBP alpha has a C/EBP binding site in its own promoter. Human C/EBP alpha autoregulates its own expression in adipocytes by activating the USF transcription factor. Myeloid genes expressed later during differentiation, such as CD11b, are also activated by PU.1, which is expressed at highest levels in mature myeloid cells, but not by C/EBP alpha, which is downregulated in a differentiated murine myeloid cell line. Consistent with this model are the findings that overexpression of PU.1 in erythroid cells blocks erythroid differentiation, leading to erythroleukemia, and overexpression of GATA-1 in a myeloid line blocks myeloid differentiation. While these findings have provided some framework for understanding myeloid gene regulation, there are a number of critical questions to be addressed in the near future: What is the pattern of expression of the C/EBP proteins during the course of myeloid differentiation and activation of human CD34+ cells? What is the effect of targeted disruption and other mutations of the C/EBP and AML1 proteins on myeloid development and receptor expression? What are the interactions among these three different types of factors (ets, basic region-zipper, and Runt domain proteins) to activate the promoters? What is the effect of translocations, mutations, and alterations in expression of these factors, particularly in different forms of AML?
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通过转录因子 PU.1 的竞争性结合抑制造血。
DOI：
10.1073/pnas.91.17.7932
发表时间：
1994
影响因子：
11.1
作者：
Voso,MT;Burn,TC;Wulf,G;Lim,B;Leone,G;Tenen,DG
通讯作者：
Tenen,DG
影响因子：
56.9
作者：
SCOTT, EW;SIMON, MC;SINGH, H
通讯作者：
SINGH, H
骨髓特异性 CD11b 启动子的表征。
影响因子：
20.3
作者：
Pahl,HL;Rosmarin,AG;Tenen,DG
通讯作者：
Tenen,DG
DOI：
10.1073/pnas.88.6.2593
发表时间：
1991-03-01
影响因子：
11.1
作者：
CHRISTY, RJ;KAESTNER, KH;LANE, MD
通讯作者：
LANE, MD
影响因子：
8
作者：
H. Chen;D. Ray-Gallet;P. Zhang;C. Hetherington;D. Gonzalez;D. Zhang;F. Moreau-Gachelin;D. Tenen
通讯作者：
H. Chen;D. Ray-Gallet;P. Zhang;C. Hetherington;D. Gonzalez;D. Zhang;F. Moreau-Gachelin;D. Tenen