Transcriptional properties of human NANOG1 and NANOG2 in acute leukemic cells.
Transcriptional properties of human NANOG1 and NANOG2 in acute leukemic cells.
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DOI：
10.1093/nar/gkq307
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发表时间：
2010-09
影响因子：
14.9
通讯作者：
Marschalek R
中科院分区：
文献类型：
--
作者：
Eberle I;Pless B;Braun M;Dingermann T;Marschalek R
NANOG和OCT 4的转录本最近已在人t（4;11）白血病和表达两种t（4;11）融合蛋白的模型系统中鉴定。此外，NANOG/OCT 4/SOX 2的下游靶基因显示出转录激活。然而，NANOG 1基因属于一个基因家族，包括一个基因串联重复（称为NANOG 2或NANOGP 1）和几个假基因（NANOGP 2-P11）。因此，尚不清楚哪些NANOG家族成员在t（4;11）白血病细胞中转录。5′-RACE实验揭示了NANOG 1和NANOG 2的新5′-外显子，其可以引起两种不同的NANOG 1和三种不同的NANOG 2蛋白变体的表达。此外，建立了一种新的基于PCR的方法，该方法允许区分来自NANOG 1、NANOG 2和所有其他NANOG假基因（P2-P11）的转录物。通过应用这种方法，我们能够证明人类造血干细胞和不同的白血病细胞转录NANOG 2。此外，我们通过在293细胞中重组表达功能性地测试了NANOG 1和NANOG 2蛋白变体。这些研究表明，NANOG 1和NANOG 2蛋白变体在功能上是等同的，并激活了激活特定干细胞基因的调节回路。因此，我们提出了这样的假设，即NANOG 2的转录激活代表了急性白血病中的“干细胞功能获得”。
Transcripts of NANOG and OCT4 have been recently identified in human t(4;11) leukemia and in a model system expressing both t(4;11) fusion proteins. Moreover, downstream target genes of NANOG/OCT4/SOX2 were shown to be transcriptionally activated. However, the NANOG1 gene belongs to a gene family, including a gene tandem duplication (named NANOG2 or NANOGP1) and several pseudogenes (NANOGP2-P11). Thus, it was unclear which of the NANOG family members were transcribed in t(4;11) leukemia cells. 5′-RACE experiments revealed novel 5′-exons of NANOG1 and NANOG2, which could give rise to the expression of two different NANOG1 and three different NANOG2 protein variants. Moreover, a novel PCR-based method was established that allows distinguishing between transcripts deriving from NANOG1, NANOG2 and all other NANOG pseudogenes (P2–P11). By applying this method, we were able to demonstrate that human hematopoietic stem cells and different leukemic cells transcribe NANOG2. Furthermore, we functionally tested NANOG1 and NANOG2 protein variants by recombinant expression in 293 cells. These studies revealed that NANOG1 and NANOG2 protein variants are functionally equivalent and activate a regulatory circuit that activates specific stem cell genes. Therefore, we pose the hypothesis that the transcriptional activation of NANOG2 represents a ‘gain-of-stem cell function’ in acute leukemia.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
影响因子：
3.4
作者：
Fairbanks DJ;Maughan PJ
通讯作者：
Maughan PJ
DOI：
10.1073/pnas.89.13.6192
发表时间：
1992-07-01
影响因子：
11.1
作者：
UDOMSAKDI, C;EAVES, CJ;EAVES, AC
通讯作者：
EAVES, AC
影响因子：
4.8
作者：
Della Ragione, F;Cucciolla, V;Zappia, V
通讯作者：
Zappia, V
影响因子：
11.5
作者：
Chumsri, Saranya;Matsui, William;Burger, Angelika M.
通讯作者：
Burger, Angelika M.