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

Young people in the world of globalization

Изучаются поведение и роль молодежи в условиях глобализации. Проводится анализ положения молодежных движений в современных условиях. На основе исторических данных и современного положения дел планируется модель развития молодежи в краткосрочном будущем.We study the behavior and the role of youth in the conditions of globalization. The article analyzes the situation of the youth movement in modern conditions. On the basis of historical data and the current status planned model of youth development in the short future

A-tract clusters may facilitate DNA packaging in bacterial nucleoid

Molecular mechanisms of bacterial chromosome packaging are still unclear, as bacteria lack nucleosomes or other apparent basic elements of DNA compaction. Among the factors facilitating DNA condensation may be a propensity of the DNA molecule for folding due to its intrinsic curvature. As suggested previously, the sequence correlations in genome reflect such a propensity [Trifonov and Sussman (1980) Proc. Natl Acad. Sci. USA, 77, 3816–3820]. To further elaborate this concept, we analyzed positioning of A-tracts (the sequence motifs introducing the most pronounced DNA curvature) in the Escherichia coli genome. First, we observed that the A-tracts are over-represented and distributed ‘quasi-regularly’ throughout the genome, including both the coding and intergenic sequences. Second, there is a 10–12 bp periodicity in the A-tract positioning indicating that the A-tracts are phased with respect to the DNA helical repeat. Third, the phased A-tracts are organized in ∼100 bp long clusters. The latter feature was revealed with the help of a novel approach based on the Fourier series expansion of the A-tract distance autocorrelation function. Since the A-tracts introduce local bends of the DNA duplex and these bends accumulate when properly phased, the observed clusters would facilitate DNA looping. Also, such clusters may serve as binding sites for the nucleoid-associated proteins that have affinities for curved DNA (such as HU, H-NS, Hfq and CbpA). Therefore, we suggest that the ∼100 bp long clusters of the phased A-tracts constitute the ‘structural code’ for DNA compaction by providing the long-range intrinsic curvature and increasing stability of the DNA complexes with architectural proteins

gamma-Selective Allylation of (E)-Alkenylzinc Iodides Prepared by Reductive Coupling of Arylacetylenes with Alkyl Iodides

The first examples of Cu-catalyzed gamma-selective allylic alkenylation using organozinc reagents are reported. (E)-Alkenylzinc iodides were prepared by Fe-catalyzed reductive coupling of terminal arylalkynes with alkyl iodides. In the presence of a copper catalyst, these reagents reacted with allylic bromides derived from Morita-Baylis-Hillman alcohols to give 1,4-dienes in high yields. The reactions are highly gamma-selective (generally gamma/alpha > 49:1) and tolerate a wide range of functional groups such as ester, cyano, keto, and nitro