A transcript profiling approach reveals the zinc finger transcription factor ZNF191 is a pleiotropic factor.
A transcript profiling approach reveals the zinc finger transcription factor ZNF191 is a pleiotropic factor.
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转录谱分析方法揭示锌指转录因子 ZNF191 是一种多效性因子
DOI：
10.1186/1471-2164-10-241
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发表时间：
2009-05-22
期刊：
影响因子：
4.4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Li J;Chen X;Gong X;Liu Y;Feng H;Qiu L;Hu Z;Zhang J
人类锌指蛋白191（ZNF 191）是Krüppel样锌指转录因子的SCAN结构域家族的成员。ZNF 191与其小鼠同源锌指蛋白191（Zfp 191）显示94%的同一性，Zfp 191是人-小鼠SCAN家族成员直向同源物对中最高度保守的。Zfp 191在早期胚胎发生和成体器官中广泛表达。此外，Zfp 191-/-胚胎已显示发育严重迟缓，大约在胚胎日龄E7.5时死亡。ZNF 191可以特异性地与酪氨酸羟化酶（TH）基因中广泛存在的HUMTH 01微卫星TCAT基序相互作用。HUMTH 01的等位基因变异对TH基因表达具有定量沉默效应，并与ZNF 191结合的定量和定性变化相关。此外，ZNF 191对转录有抑制作用，但下游靶点很少。我们在人胚肾（HEK 293）细胞中使用瞬时过表达和敲低策略寻找ZNF 191靶基因。微阵列分析确定了6094个基因的过表达的ZNF 191和3332个基因的ZNF 191的敲低调控，使用的阈值为1.2倍。经真实的时间RT-PCR验证，几个感兴趣的候选基因与芯片数据相关性良好。有趣的是，在瞬时过表达和瞬时敲低策略中鉴定了1456个基因。GenMAPP和Mapparent软件包进一步用于这些显著改变的基因的途径分析。研究发现，一些基因通路参与了激酶活性的调节、转录、血管生成、脑发育和对DNA损伤的反应。我们的分析首次揭示了ZNF 191是一种多效性因子，在造血、脑发育和癌症中发挥作用。
The human zinc finger protein 191 (ZNF191) is a member of the SCAN domain family of Krüppel-like zinc finger transcription factors. ZNF191 shows 94% identity to its mouse homologue zinc finger protein 191(Zfp191), which is the most highly conserved among the human-mouse SCAN family member orthologues pairs. Zfp191 is widely expressed during early embryogenesis and in adult organs. Moreover, Zfp191-/- embryos have been shown to be severely retarded in development and die approximately at embryonic day E7.5. ZNF191 can specifically interact with the widespread TCAT motif which constitutes the HUMTH01 microsatellite in the tyrosine hydroxylase (TH) gene. Allelic variations of HUMTH01 have been stated to have a quantitative silencing effect on TH gene expression and to correlate with quantitative and qualitative changes in the binding by ZNF191. In addition, ZNF191 displays a suppressive effect on the transcription; however, little downstream targets have identified. We searched for ZNF191 target genes by using a transient overexpression and knockdown strategy in the human embryo kidney (HEK293) cells. Microarray analyses identified 6094 genes modulated by overexpression of ZNF191 and 3332 genes regulated by knockdown of ZNF191, using a threshold of 1.2-fold. Several interested candidate genes, validated by real time RT-PCR, were correlated well with the array data. Interestingly, 1456 genes were identified in both transient overexpression and transient knockdown strategies. The GenMAPP and MappFinder software packages were further used for pathway analysis of these significantly altered genes. Several gene pathways were found to be involved in processes of the regulation of kinase activity, transcription, angiogenesis, brain development and response to DNA damage. Our analysis reveals for the first time that ZNF191 is a pleiotropic factor that has a role in hematopoiesis, brain development and cancers.
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影响因子：
12.3
作者：
Kaczynski J;Cook T;Urrutia R
通讯作者：
Urrutia R
影响因子：
4.8
作者：
Adachi, H;Tsujimoto, M
通讯作者：
Tsujimoto, M
影响因子：
1.2
作者：
Khalfallah, Olfa;Faucon-Biguet, Nicole;Mallet, Jacques
通讯作者：
Mallet, Jacques
DOI：
10.1073/pnas.88.9.3608
发表时间：
1991-05-01
影响因子：
11.1
作者：
BELLEFROID, EJ;PONCELET, DA;MARTIAL, JA
通讯作者：
MARTIAL, JA
影响因子：
11.2
作者：
Harper, Jav;Yan, Li;Moses, Marsha A.
通讯作者：
Moses, Marsha A.