Enhanced binding of poly(ADP-ribose)polymerase-1 and Ku80/70 to the ITGA2 promoter via an extended cytosine-adenosine repeat.
Enhanced binding of poly(ADP-ribose)polymerase-1 and Ku80/70 to the ITGA2 promoter via an extended cytosine-adenosine repeat.
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DOI：
10.1371/journal.pone.0008743
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发表时间：
2010-01-15
期刊：
影响因子：
3.7
通讯作者：
Kunicki TJ
中科院分区：
文献类型：
--
作者：
Cheli Y;Williams SA;Ballotti R;Nugent DJ;Kunicki TJ
我们在人整合素α2基因ITGA2的5‘-调控区发现了一种胞嘧啶-腺苷(CA)重复长度多态性，该基因起始于−605。我们的目标是确定该多态性对整合素α-2-β-1表达的调节作用，并探讨其可能的机制(S)。结合先前被我们确定为转录因子Sp1结合位点的SNP C-52T，可以区分出四种ITGA2单倍型，按照它们促进ITGA2转录的顺序：(CA)12/-52C>；(CA)11/-52C>；(CA)11/-52T>；(CA)10/-52T.通过DNA亲和层析和染色质免疫沉淀(ChIP)分析，我们发现聚(ADP-核糖)聚合酶-1(PARP-1)和Ku80/70与较长的(CA)12重复等位基因特异性结合，亲和力增强。转录共激活复合体的已知成分PARP-1和KU80/70与ITGA2的较长(CA)12等位基因结合增加与α2β1表达增强一致。对这些发现最有可能的解释是PARP-1和Ku80/70参与了ITGA2的转录调控。这些观察结果为人类血小板和其他细胞中整合素α2β1表达的单倍型依赖变异性提供了新的见解(S)。
We have identified a cytosine-adenosine (CA) repeat length polymorphism in the 5′-regulatory region of the human integrin α2 gene ITGA2 that begins at −605. Our objective was to establish the contribution of this polymorphism to the regulation of integrin α2β1 expression, which is known to vary several-fold among normal individuals, and to investigate the underlying mechanism(s). In combination with the SNP C-52T, previously identified by us as a binding site for the transcription factor Sp1, four ITGA2 haplotypes can be distinguished, in the order in which they enhance ITGA2 transcription: (CA)12/-52C>(CA)11/-52C>(CA)11/-52T>(CA)10/-52T. By DNA affinity chromatography and chromatin immunoprecipitation (ChIP) assays, we show that poly (ADP-ribose)polymerase-1 (PARP-1) and Ku80/70 bind specifically and with enhanced affinity to the longer (CA)12 repeat alleles. The increased binding of PARP-1 and Ku80/70, known components of transcription co-activator complexes, to the longer (CA)12 alleles of ITGA2 coincides with enhanced α2β1 expression. The most likely explanation for these findings is that PARP-1 and Ku80/70 contribute to the transcriptional regulation of ITGA2. These observations provide new insight into the mechanisms(s) underlying haplotype-dependent variability in integrin α2β1 expression in human platelets and other cells.
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将聚（ADP-核糖）聚合酶-1和KU70/KU80鉴定为S100A9基因表达的转录调节剂。
影响因子：
--
作者：
Grote, Jens;Koenig, Simone;Ackermann, Doreen;Sopalla, Claudia;Benedyk, Malgorzata;Los, Marek;Kerkhoff, Claus
通讯作者：
Kerkhoff, Claus
影响因子：
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作者：
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通讯作者：
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影响因子：
10.4
作者：
Kunicki, T. J.;Williams, S. A.;Nugent, D. J.
通讯作者：
Nugent, D. J.
DOI：
10.1073/pnas.94.6.2261
发表时间：
1997-03-18
影响因子：
11.1
作者：
Meisterernst, M;Stelzer, G;Roeder, RG
通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
Tainsky, MA