Associations between intronic non-B DNA structures and exon skipping.

Non-B DNA structures are abundant in the genome and are often associated with critical biological processes, including gene regulation, chromosome rearrangement and genome stabilization. In particular, G-quadruplex (G4) may affect alternative splicing based on its ability to impede the activity of RNA polymerase II. However, the specific role of non-B DNA structures in splicing regulation still awaits investigation. Here, we provide a genome-wide and cross-species investigation of the associations between five non-B DNA structures and exon skipping. Our results indicate a statistically significant correlation of each examined non-B DNA structures with exon skipping in both human and mouse. We further show that the contributions of non-B DNA structures to exon skipping are influenced by the occurring region. These correlations and contributions are also significantly different in human and mouse. Finally, we detailed the effects of G4 by showing that occurring on the template strand and the length of G-run, which is highly related to the stability of a G4 structure, are significantly correlated with exon skipping activity. We thus show that, in addition to the well-known effects of RNA and protein structure, the relative positional arrangement of intronic non-B DNA structures may also impact exon skipping.

3,4-Dimeth-oxy-4'-nitro-1,1'-biphen-yl.

The title compound, C(14)H(13)NO(4), was prepared through a palladium-catalysed Suzuki-Miyaura coupling reaction. The asymmetric unit comprises two mol-ecules related by pseudo-inversion symmetry. The dihedral angles between the benzene rings in the two mol-ecules are 44.30 (6) and 48.50 (6)° while those between the benzene ring and the nitro group are 6.54 (13) and 5.73 (10)°. The crystal packing is defined only by Van der Waals inter-actions.

3',4'-Dimeth-oxy-biphenyl-4-carbonitrile.

The title compound, C(15)H(13)NO(2), was prepared through a palladium-catalysed Suzuki-Miyaura coupling reaction. The dihedral angle between the biphenyl rings is 40.96 (6)°. The meth-oxy groups are twisted slightly out of the plane of the benzene ring [C-C-C-C torsion angles = -3.61 (18) and 12.6 (2)°]. The packing of the molecules is stabilized by van der Waals inter-actions.

2,9,10-Trimeth-oxy-dibenzo[b,d]oxepin-7(6H)-one.

The title compound, C(17)H(16)O(5), was prepared through a cyclization reaction of 2-(3',4',5-trimeth-oxy-biphenyl-2-yl-oxy)acetyl chloride. The two benzene rings form a dihedral angle of 34.55 (5)°. The crystal structure does not feature any hydrogen bonds.

3a,11b-Dihy-droxy-3a,11b-dihydro-1H-imidazo[4,5-f][1,10]phenanthroline-2(3H)-thione.

The title compound, C(13)H(10)N(4)O(2)S, was prepared through a cyclization reaction of 1,10-phenanthroline-5,6-dione and thio-urea. The dihedral angle between the pyridine rings is 8.22 (2)°. In the crystal, mol-ecules are connected by N-H⋯O, O-H⋯N, N-H⋯S and O-H⋯S hydrogen bonds, forming a three-dimensional network.

Evidence of association between nucleosome occupancy and the evolution of transcription factor binding sites in yeast.

BACKGROUND: Divergence of transcription factor binding sites is considered to be an important source of regulatory evolution. The associations between transcription factor binding sites and phenotypic diversity have been investigated in many model organisms. However, the understanding of other factors that contribute to it is still limited. Recent studies have elucidated the effect of chromatin structure on molecular evolution of genomic DNA. Though the profound impact of nucleosome positions on gene regulation has been reported, their influence on transcriptional evolution is still less explored. With the availability of genome-wide nucleosome map in yeast species, it is thus desirable to investigate their impact on transcription factor binding site evolution. Here, we present a comprehensive analysis of the role of nucleosome positioning in the evolution of transcription factor binding sites. RESULTS: We compared the transcription factor binding site frequency in nucleosome occupied regions and nucleosome depleted regions in promoters of old (orthologs among Saccharomycetaceae) and young (Saccharomyces specific) genes; and in duplicate gene pairs. We demonstrated that nucleosome occupied regions accommodate greater binding site variations than nucleosome depleted regions in young genes and in duplicate genes. This finding was confirmed by measuring the difference in evolutionary rates of binding sites in sensu stricto yeasts at nucleosome occupied regions and nucleosome depleted regions. The binding sites at nucleosome occupied regions exhibited a consistently higher evolution rate than those at nucleosome depleted regions, corroborating the difference in the selection constraints at the two regions. Finally, through site-directed mutagenesis experiment, we found that binding site gain or loss events at nucleosome depleted regions may cause more expression differences than those in nucleosome occupied regions. CONCLUSIONS: Our study indicates the existence of different selection constraint on binding sites at nucleosome occupied regions than at the nucleosome depleted regions. We found that the binding sites have a different rate of evolution at nucleosome occupied and depleted regions. Finally, using transcription factor binding site-directed mutagenesis experiment, we confirmed the difference in the impact of binding site changes on expression at these regions. Thus, our work demonstrates the importance of composite analysis of chromatin and transcriptional evolution.

4-Meth-oxy-2-nitro-4'-(trifluoro-meth-yl)biphen-yl.

The title compound, C(14)H(10)F(3)NO(3), was prepared by a palladium-catalysed Suzuki-Miyaura coupling reaction. The dihedral angle between the nitro group and its parent benzene ring is 66.85 (19)° while the dihedral angle between the two benzene rings is 49.98 (9)°. The CF(3) group is disordered over two sets of sites with occupancies of 0.457 (8) and 0.543 (8).

Ethyl N-[3-(N,N-dimethyl-carbamo-yl)pyridin-2-ylsulfon-yl]carbamate.

In the mol-ecular structure of the title compound, C(11)H(15)N(3)O(5)S, the amide group is nearly perpendicular to the pyridine ring, making a dihedral angle of 86.30 (13)°. The terminal ethyl group is disordered over two sites of equal occupancy. Inter-molecular N-H⋯O hydrogen bonding is present in the crystal structure.

Methyl 4-methyl-sulfonyl-2-nitro-benzoate.

The title compound, C(9)H(9)NO(6)S, was prepared by the reaction of methanol and thionyl chloride with 4-methyl-sulfonyl-2-nitro-benzoic acid under mild conditions. The dihedral angle between the nitro group and benzene ring is 21.33 (19)° and that between the carboxyl-ate group and the benzene ring is 72.09 (17)°. The crystal structure is stabilized by weak inter-molecular bifurcated C-H⋯O inter-actions occurring in the (100) plane.

ProteDNA: a sequence-based predictor of sequence-specific DNA-binding residues in transcription factors.

This article presents the design of a sequence-based predictor named ProteDNA for identifying the sequence-specific binding residues in a transcription factor (TF). Concerning protein-DNA interactions, there are two types of binding mechanisms involved, namely sequence-specific binding and nonspecific binding. Sequence-specific bindings occur between protein sidechains and nucleotide bases and correspond to sequence-specific recognition of genes. Therefore, sequence-specific bindings are essential for correct gene regulation. In this respect, ProteDNA is distinctive since it has been designed to identify sequence-specific binding residues. In order to accommodate users with different application needs, ProteDNA has been designed to operate under two modes, namely, the high-precision mode and the balanced mode. According to the experiments reported in this article, under the high-precision mode, ProteDNA has been able to deliver precision of 82.3%, specificity of 99.3%, sensitivity of 49.8% and accuracy of 96.5%. Meanwhile, under the balanced mode, ProteDNA has been able to deliver precision of 60.8%, specificity of 97.6%, sensitivity of 60.7% and accuracy of 95.4%. ProteDNA is available at the following websites: http://protedna.csbb.ntu.edu.tw/, http://protedna.csie.ntu.edu.tw/, http://bio222.esoe.ntu.edu.tw/ProteDNA/.