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Background  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).    Methodology/Principal Findings  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.    Conclusions/Significance  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.

Enhanced Binding of Poly(ADP-ribose)polymerase-1 and Ku80/70 to the ITGA2 Promoter via an Extended Cytosine-Adenosine Repeat