Role of DNA sequence based structural features of promoters in transcription initiation and gene expression

Bansal, Manju; Kumar, Aditya; Yella, Venkata Rajesh

doi:10.1016/j.sbi.2014.01.007

Cited by 85 publications

(94 citation statements)

References 80 publications

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“…The mobility differences observed for oligomers A4T1in(0) to A4T1in (11) are plotted in Fig. 4 as a function of the number of flanking A$T basepairs.…”

Section: The Mobility Differences Observed For a Given A-tract Are Momentioning

confidence: 99%

“…DNA A-tracts have been the focus of much attention in recent years because they are overrepresented in genomic DNA (10) and are found near many origins of replication and transcription factor binding sites (5,(10)(11)(12). However, the biological role of DNA A-tracts in the cell is not well understood (5), most likely because the B* conformation is in rapid equilibrium with normal B-DNA under physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

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Flanking A·T Basepairs Destabilize the B∗ Conformation of DNA A-Tracts

Stellwagen

2015

Biophysical Journal

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Capillary electrophoresis has been used to characterize the interaction of monovalent cations with 26-basepair DNA oligomers containing A-tracts embedded in flanking sequences with different basepair compositions. A 26-basepair random-sequence oligomer was used as the reference; lithium and tetrabutylammonium (TBA(+)) ions were used as the probe ions. The free solution mobilities of the A-tract and random-sequence oligomers were identical in solutions containing <∼ 100 mM cation. At higher cation concentrations, the A-tract oligomers migrated faster than the reference oligomer in TBA(+) and slower than the reference in Li(+). Hence, cations of different sizes can interact very differently with DNA A-tracts. The increased mobilities observed in TBA(+) suggest that the large hydrophobic TBA(+) ions are preferentially excluded from the vicinity of the A-tract minor groove, increasing the effective net charge of the A-tract oligomers and increasing the mobility. By contrast, Li(+) ions decrease the mobility of A-tract oligomers because of the preferential localization of Li(+) ions in the narrow A-tract minor groove. Embedding the A-tracts in AT-rich flanking sequences markedly alters preferential interactions of monovalent cations with the B(∗) conformation. Hence, A-tracts embedded in genomic DNA may or may not interact preferentially with monovalent cations, depending on the relative number of A · T basepairs in the flanking sequences.

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“…The mobility differences observed for oligomers A4T1in(0) to A4T1in (11) are plotted in Fig. 4 as a function of the number of flanking A$T basepairs.…”

Section: The Mobility Differences Observed For a Given A-tract Are Momentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Flanking A·T Basepairs Destabilize the B∗ Conformation of DNA A-Tracts

Stellwagen

2015

Biophysical Journal

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“…37,43 Despite their well demonstrated biochemical roles in transcription, their structural roles have only been suggested. 8,27,44,45 Here we examine such structural effects of variable NRL at the apex of a 125 nucleosome loop by adjusting linker lengths to match the recently characterized ‘wide’ NFRs reported in bivalent embryonic stem cell genes by Dieuleveult et. al.…”

Section: Introductionmentioning

confidence: 99%

Mesoscale Modeling Reveals Hierarchical Looping of Chromatin Fibers Near Gene Regulatory Elements

2016

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While it is well recognized that chromatin loops play an important role in gene regulation, structural details regarding higher order chromatin loops are only emerging. Here we present a systematic study of restrained chromatin loops ranging from 25–427 nucleosomes (fibers of 5–80 Kb DNA in length), mimicking gene elements studied by 3C contact data. We find that hierarchical looping represents a stable configuration that can efficiently bring distant regions of the GATA-4 gene together, satisfying connections reported by 3C experiments. Additionally, we find that restrained chromatin fibers larger than 100 nucleosomes (~20Kb) form closed plectonemes, whereas fibers shorter than 100 nucleosomes form simple hairpin loops. By studying the dependence of loop structures on internal parameters, we show that loop features are sensitive to linker histone concentration, loop length, divalent ions, and DNA linker length. Specifically, increasing loop length, linker histone concentration, and divalent ion concentration is associated with increased persistence length (or decreased bending), while varying DNA linker length in a manner similar to experimentally observed ‘Nucleosome Free Regions’ (found near transcription start sites) disrupts intertwining and leads to loop opening and increased persistence length in linker histone depleted (−LH) fibers. Chromatin fiber structure sensitivity to these parameters, all of which vary throughout cell cycle, across tissue type and across species, suggests that caution is warranted when using uniform polymer models to fit chromatin conformation capture genome-wide data. Furthermore, the folding geometry we observe near the transcription initiation site of the GATA-4 gene suggests that hierarchical looping provides a structural mechanism for gene inhibition, and offers tunable parameters for design of gene regulation elements.

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“…Earlier studies (48,49), have implicated base sequence dependent shape and electrostatic potential in the grooves of DNA, as well as DNA curvature and bendability (50) in molecular function. The present study provides us with additional information imprinted in the DNA sequences, suggestive of a plausible physico-chemical property based mechanism of read-out of DNA function.…”

Section: Resultsmentioning

confidence: 99%

Physico-chemical fingerprinting of RNA genes

Singh

Mishra

Khosravi

et al. 2016

Nucleic Acids Research

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We advance here a novel concept for characterizing different classes of RNA genes on the basis of physico-chemical properties of DNA sequences. As knowledge-based approaches could yield unsatisfactory outcomes due to limitations of training on available experimental data sets, alternative approaches that utilize properties intrinsic to DNA are needed to supplement training based methods and to eventually provide molecular insights into genome organization. Based on a comprehensive series of molecular dynamics simulations of Ascona B-DNA consortium, we extracted hydrogen bonding, stacking and solvation energies of all combinations of DNA sequences at the dinucleotide level and calculated these properties for different types of RNA genes. Considering ∼7.3 million mRNA, 255 524 tRNA, 40 649 rRNA (different subunits) and 5250 miRNA, 3747 snRNA, gene sequences from 9282 complete genome chromosomes of all prokaryotes and eukaryotes available at NCBI, we observed that physico-chemical properties of different functional units on genomic DNA differ in their signatures.

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Role of DNA sequence based structural features of promoters in transcription initiation and gene expression

Cited by 85 publications

References 80 publications

Flanking A·T Basepairs Destabilize the B∗ Conformation of DNA A-Tracts

Flanking A·T Basepairs Destabilize the B∗ Conformation of DNA A-Tracts

Mesoscale Modeling Reveals Hierarchical Looping of Chromatin Fibers Near Gene Regulatory Elements

Physico-chemical fingerprinting of RNA genes

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