Impact of Alu repeats on the evolution of human p53 binding sites

<p>Abstract</p> <p>Background</p> <p>The p53 tumor suppressor protein is involved in a complicated regulatory network, mediating expression of ~1000 human genes. Recent studies have shown that many p53 <it>in vivo </it>binding sites (BSs) reside in transposable repeats. The relationship between these BSs and functional p53 response elements (REs) remains unknown, however. We sought to understand whether the p53 REs also reside in transposable elements and particularly in the most-abundant Alu repeats.</p> <p>Results</p> <p>We have analyzed ~160 functional p53 REs identified so far and found that 24 of them occur in repeats. More than half of these repeat-associated REs reside in Alu elements. In addition, using a position weight matrix approach, we found ~400,000 potential p53 BSs in Alu elements genome-wide. Importantly, these putative BSs are located in the same regions of Alu repeats as the functional p53 REs - namely, in the vicinity of Boxes A/A' and B of the internal RNA polymerase III promoter. Earlier nucleosome-mapping experiments showed that the Boxes A/A' and B have a different chromatin environment, which is critical for the binding of p53 to DNA. Here, we compare the Alu-residing p53 sites with the corresponding Alu consensus sequences and conclude that the p53 sites likely evolved through two different mechanisms - the sites overlapping with the Boxes A/A' were generated by CG → TG mutations; the other sites apparently pre-existed in the progenitors of several Alu subfamilies, such as AluJo and AluSq. The binding affinity of p53 to the Alu-residing sites generally correlates with the age of Alu subfamilies, so that the strongest sites are embedded in the 'relatively young' Alu repeats.</p> <p>Conclusions</p> <p>The primate-specific Alu repeats play an important role in shaping the p53 regulatory network in the context of chromatin. One of the selective factors responsible for the frequent occurrence of Alu repeats in introns may be related to the p53-mediated regulation of Alu transcription, which, in turn, influences expression of the host genes.</p> <p>Reviewers</p> <p>This paper was reviewed by Igor B. Rogozin (nominated by Pavel A. Pevzner), Sandor Pongor, and I. King Jordan.</p

The 4π4\pi-fragment-spectrometer FOBOS

The 4 π - fragment - spectrometer FOBOS developed for heavy-ion research at beam energies of 10 - 100 AMeV has been commissioned for physical experiments at the Flerov Laboratory of Nuclear Reactions of the Joint Institute for Nuclear Research in Dubna. Based on the logarithmic detector principle, it is able to register charged fragments from Protons up to heavy residual nuclei in a large dynamical range. Position-sensitive avalanche counters, axial ionization chambers and CsI(TI) scintillation detectors are arranged in three concentric detector shells. An array of phoswich detectors is used as a more granular forward detector at narrow polar angles. The modular concept of FOBOS allows for different experimental application in the field of exclusive fragment spectroscopy at medium multiplicities. For illustration the fragment spectroscopy studies concerning the spontaneous fission process and the fragmentation of hot nuclei by means of the FOBOS set-up are considered