Weighted gene co-expression network analysis of nitrogen (N)-responsive genes and the putative role of G-quadruplexes in N use efficiency (NUE) in rice.

Rice is an important target to improve crop nitrogen (N) use efficiency (NUE), and the identification and shortlisting of the candidate genes are still in progress. We analyzed data from 16 published N-responsive transcriptomes/microarrays to identify, eight datasets that contained the maximum number of 3020 common genes, referred to as N-responsive genes. These include different classes of transcription factors, transporters, miRNA targets, kinases and events of post-translational modifications.

Convergent evolution of a genomic rearrangement may explain cancer resistance in hystrico- and sciuromorpha rodents.

The rodents of hystricomorpha and sciuromorpha suborders exhibit remarkably lower incidence of cancer. The underlying genetic basis remains obscure. We report a convergent evolutionary split of human 3p21.

CTCF-Mediated Genome Architecture Regulates the Dosage of Mitotically Stable Mono-allelic Expression of Autosomal Genes.

The mechanisms that guide the clonally stable random mono-allelic expression of autosomal genes remain enigmatic. We show that (1) mono-allelically expressed (MAE) genes are assorted and insulated from bi-allelically expressed (BAE) genes through CTCF-mediated chromatin loops; (2) the cell-type-specific dynamics of mono-allelic expression coincides with the gain and loss of chromatin insulator sites; (3) dosage of MAE genes is more sensitive to the loss of chromatin insulation than that of BAE genes; and (4) inactive alleles of MAE genes are significantly more insulated than active alleles and are de-repressed upon CTCF depletion. This alludes to a topology wherein the inactive alleles of MAE genes are insulated from the spatial interference of transcriptional states from the neighboring bi-allelic domains via CTCF-mediated loops.

Biased visibility in Hi-C datasets marks dynamically regulated condensed and decondensed chromatin states genome-wide.

Background: Proximity ligation based techniques, like Hi-C, involve restriction digestion followed by ligation of formaldehyde cross-linked chromatin. Distinct chromatin states can impact the restriction digestion, and hence the visibility in the contact maps, of engaged loci. Yet, the extent and the potential impact of digestion bias remain obscure and under-appreciated in the literature.

Does genome surveillance explain the global discrepancy between binding and effect of chromatin factors?

Knocking out a chromatin factor often does not alter the transcription of its binding targets. What explains the observed disconnect between binding and effect? We hypothesize that this discrepancy could be associated with the role of chromatin factors in maintaining genetic and epigenetic integrity at promoters, and not necessarily with transcription. Through re-analysis of published datasets, we present several lines of evidence that support our hypothesis and deflate the popular assumptions.

Yeast PAF1 complex counters the pol III accumulation and replication stress on the tRNA genes.

The RNA polymerase (pol) III transcribes mostly short, house-keeping genes, which produce stable, non-coding RNAs. The tRNAs genes, highly transcribed by pol III in vivo are known replication fork barriers. One of the transcription factors, the PAF1C (RNA polymerase II associated factor 1 complex) is reported to associate with pol I and pol II and influence their transcription.

Evolutionary Loss of Genomic Proximity to Conserved Noncoding Elements Impacted the Gene Expression Dynamics During Mammalian Brain Development.

Conserved noncoding elements (CNEs) have a significant regulatory influence on their neighboring genes. Loss of proximity to CNEs through genomic rearrangements can, therefore, impact the transcriptional states of the cognate genes. Yet, the evolutionary implications of such chromosomal alterations have not been studied.

Spatially coordinated replication and minimization of expression noise constrain three-dimensional organization of yeast genome.

Despite recent advances, the underlying functional constraints that shape the three-dimensional organization of eukaryotic genome are not entirely clear. Through comprehensive multivariate analyses of genome-wide datasets, we show that cis and trans interactions in yeast genome have significantly distinct functional associations. In particular, (i) the trans interactions are constrained by coordinated replication and co-varying mutation rates of early replicating domains through interactions among early origins, while cis interactions are constrained by coordination of late replication through interactions among late origins; (ii)cis and trans interactions exhibit differential preference for nucleosome occupancy; (iii)cis interactions are also constrained by the essentiality and co-fitness of interacting genes.

Evolutionarily conserved and conformationally constrained short peptides might serve as DNA recognition elements in intrinsically disordered regions.

Despite recent advances, it is yet not clear how intrinsically disordered regions in proteins recognize their targets without any defined structures. Short linear motifs had been proposed to mediate molecular recognition by disordered regions; however, the underlying structural prerequisite remains elusive. Moreover, the role of short linear motifs in DNA recognition has not been studied.

DNase I-hypersensitive exons colocalize with promoters and distal regulatory elements.

The precise splicing of genes confers an enormous transcriptional complexity to the human genome. The majority of gene splicing occurs cotranscriptionally, permitting epigenetic modifications to affect splicing outcomes. Here we show that select exonic regions are demarcated within the three-dimensional structure of the human genome.

Large-scale functional organization of long-range chromatin interaction networks.

Chromatin interactions play important roles in transcription regulation. To better understand the underlying evolutionary and functional constraints of these interactions, we implemented a systems approach to examine RNA polymerase-II-associated chromatin interactions in human cells. We found that 40% of the total genomic elements involved in chromatin interactions converged to a giant, scale-free-like, hierarchical network organized into chromatin communities.

Did the modulation of expression noise shape the evolution of three dimensional genome organizations in eukaryotes?

The pervasive role of distant chromatin interactions in transcriptional regulation is increasingly becoming evident. There is a possibility that the greater diversity in chromatin interactions of a genomic locus could contribute to stochastic variation in its gene expression. However, this issue has not been addressed.

Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation.

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIA-PET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions.

Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function: hypotheses and a comprehensive review.

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into 'cumulus-type', i.

Female-biased expression of long non-coding RNAs in domains that escape X-inactivation in mouse.

Background: Sexual dimorphism in brain gene expression has been recognized in several animal species. However, the relevant regulatory mechanisms remain poorly understood. To investigate whether sex-biased gene expression in mammalian brain is globally regulated or locally regulated in diverse brain structures, and to study the genomic organisation of brain-expressed sex-biased genes, we performed a large scale gene expression analysis of distinct brain regions in adult male and female mice.

Systems properties of proteins encoded by imprinted genes.

Genomically imprinted genes show parentally fixed mono-allelic expression and are important for the mammalian development. Dysregulation of genomic imprinting leads to several complex pathological conditions. Though the genetic and epigenetic regulation of imprinted genes has been well studied, their protein aspects are largely ignored.

Nonallelic transvection of multiple imprinted loci is organized by the H19 imprinting control region during germline development.

Recent observations highlight that the mammalian genome extensively communicates with itself via long-range chromatin interactions. The causal link between such chromatin cross-talk and epigenetic states is, however, poorly understood. We identify here a network of physically juxtaposed regions from the entire genome with the common denominator of being genomically imprinted.

GASCO: genetic algorithm simulation for codon optimization.

Codon optimization is a generic technique to achieve optimum expression of a foreign gene in the host's cell system. Selection of optimum codons depends on codon usage of the host genome and the presence of several desirable and undesirable sequence motifs. Searching these motifs in all possible combinations of the codons increases the search space exponentially with respect to sequence length.

Intrinsic disorder explains diverse nuclear roles of chromatin remodeling proteins.

Chromatin remodelers, a group of proteins involved in nucleosome re-positioning and modification, have extensive range of interacting partners. They form multimeric complexes and interact with modified histones, transcription, splicing, and replication factors, DNA, RNA, and the factors related to the maintenance of chromosome structure. Such diverse range of interactions is hard to explain with the presumed highly structured form of the protein.

Spirulina nitrate-assimilating enzymes (NR, NiR, GS) have higher specific activities and are more stable than those of rice.

Spirulina platensis, a cyanobacterium whose N-metabolic pathway is similar to that of higher plants like rice (Oryza sativa), produces tenfold more protein, indicating a higher capacity for nitrate utilization/removal. Our in vitro analyses in crude extracts revealed that this can be attributed, at least in part, to the higher specific activities (3-6 fold) and half lives (1.2-4.

Structural assessment of glycyl mutations in invariantly conserved motifs.

Motifs that are evolutionarily conserved in proteins are crucial to their structure and function. In one of our earlier studies, we demonstrated that the conserved motifs occurring invariantly across several organisms could act as structural determinants of the proteins. We observed the abundance of glycyl residues in these invariantly conserved motifs.

Dynamic alpha-helices: conformations that do not conform.

Structural transitions are important for the stability and function of proteins, but these phenomena are poorly understood. An extensive analysis of Protein Data Bank entries reveals 103 regions in proteins with a tendency to transform from helical to nonhelical conformation and vice versa. We find that these dynamic helices, unlike other helices, are depleted in hydrophobic residues.

A whole genome analysis of 5' regulatory regions of human genes for putative cis-acting modulators of nucleosome positioning.

We have carried out in silico analysis of upstream regions of 23,034 genes from the human genome for sequence motifs, which can potentially affect nucleosome positioning. Nucleosome exclusion elements (NEE) occur in 12% of the genes while less than 1% contain nucleosome positioning elements (NPE). NEE are significantly higher in 5' regions of certain categories of genes, namely, genes with active promoters, genes localised to gene-rich chromosomes 16, 17 and 19, genes having significantly higher expression levels and higher levels of occupancy of general transcription machinery proteins.

Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions.

Accumulating evidence converges on the possibility that chromosomes interact with each other to regulate transcription in trans. To systematically explore the epigenetic dimension of such interactions, we devised a strategy termed circular chromosome conformation capture (4C). This approach involves a circularization step that enables high-throughput screening of physical interactions between chromosomes without a preconceived idea of the interacting partners.

Conformational flexibility may explain multiple cellular roles of PEST motifs.

PEST sequences are one of the major motifs that serve as signal for the protein degradation and are also involved in various cellular processes such as phosphorylation and protein-protein interaction. In our earlier study, we found that these motifs contribute largely to eukaryotic protein disorder. This observation led us to evaluate their conformational variability in the nonredundant Protein Data Bank (PDB) structures.