| First Author | Katz DJ | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 10 | Pages | 3855-63 |
| PubMed ID | 15870260 | Mgi Jnum | J:98880 |
| Mgi Id | MGI:3580200 | Doi | 10.1128/MCB.25.10.3855-3863.2005 |
| Citation | Katz DJ, et al. (2005) Functional characterization of a novel Ku70/80 pause site at the H19/Igf2 imprinting control region. Mol Cell Biol 25(10):3855-63 |
| abstractText | The imprinted expression of the H19 and Igf2 genes in the mouse is controlled by an imprinting control center (ICR) whose activity is regulated by parent-of-origin differences in methylation. The only protein that has been implicated in ICR function is the zinc-finger protein CTCF, which binds at multiple sites within the maternally inherited ICR and is required to form a chromatin boundary that inhibits Igf2 expression. To identify other proteins that play a role in imprinting, we employed electrophoresis mobility shift assays to identify two novel binding sites within the ICR. The DNA binding activity was identified as the heterodimer Ku70/80, which binds nonspecifically to free DNA ends. The sites within the ICR bind Ku70/80 in a sequence-specific manner and with higher affinity than previously reported binding sites. The binding required the presence of Mg(2+), implying that the sequence is a pause site for Ku70/80 translocation from a free end. Chromatin immunoprecipitation assays were unable to confirm that Ku70/80 binds to the ICR in vivo. In addition, mutation of these binding sites in the mouse did not result in any imprinting defects. A genome scan revealed that the binding site is found in LINE-1 retrotransposons, suggesting a possible role for Ku70/80 in transposition. |
