A Multigraph-Based Representation of Hi-C Data.

Chromatin-chromatin interactions and three-dimensional (3D) spatial structures are involved in transcriptional regulation and have a decisive role in DNA replication and repair. To understand how individual genes and their regulatory elements function within the larger genomic context, and how the genome reacts to environmental stimuli, the linear sequence information needs to be interpreted in three-dimensional space, which is still a challenging task. Here, we propose a novel, heuristic approach to represent Hi-C datasets by a whole-genomic pseudo-structure in 3D space. The baseline of our approach is the construction of a multigraph from genomic-sequence data and Hi-C interaction data, then applying a modified force-directed layout algorithm. The resulting layout is a pseudo-structure. While pseudo-structures are not based on direct observation and their details are inherent to settings, surprisingly, they demonstrate interesting, overall similarities of known genome structures of both barley and rice, namely, the Rabl and Rosette-like conformation. It has an exciting potential to be extended by additional omics data (RNA-seq, Chip-seq, etc.), allowing to visualize the dynamics of the pseudo-structures across various tissues or developmental stages. Furthermore, this novel method would make it possible to revisit most Hi-C data accumulated in the public domain in the last decade.

The advent of electrophilic hydroxylamine-derived reagents for the direct preparation of unprotected amines.

Electrophilic aminating reagents have seen a renaissance in recent years as effective nitrogen sources for the synthesis of unprotected amino functionalities. Based on their reactivity, several noble and non-noble transition metal catalysed amination reactions have been developed. These include the aziridination and difunctionalisation of alkenes, the amination of arenes as well as the synthesis of aminated sulfur compounds. In particular, the use of hydroxylamine-derived (N-O) reagents, such as PONT (PivONH3OTf), has enabled the introduction of unprotected amino groups on various different feedstock compounds, such as alkenes, arenes and thiols. This strategy obviates undesired protecting-group manipulations and thus improves step efficiency and atom economy. Overall, this feature article gives a recent update on several reactions that have been unlocked by employing versatile hydroxylamine-derived aminating reagents, which facilitate the generation of unprotected primary, secondary and tertiary amino groups.

Hydroxylamine-Derived Reagent as a Dual Oxidant and Amino Group Donor for the Iron-Catalyzed Preparation of Unprotected Sulfinamides from Thiols.

An iron catalyzed reaction for the selective transformation of thiols (-SH) to sulfinamides (-SONH2 ) by a direct transfer of -O and free -NH2 groups has been developed. The reaction operates under mild conditions using a bench stable hydroxylamine derived reagent, exhibits broad functional group tolerance, is scalable and proceeds without the use of any precious metal catalyst or additional oxidant. This novel, practical reaction leads to the formation of two distinct new bonds (S=O and S-N) in a single step to chemoselectively form valuable, unprotected sulfinamide products. Preliminary mechanistic studies implicate the role of the alcoholic solvent as an oxygen atom donor.

Direct Synthesis of Unprotected 2-Azidoamines from Alkenes via an Iron-Catalyzed Difunctionalization Reaction.

Unprotected, primary 2-azidoamines are versatile precursors to vicinal diamines, which are among the most common motifs in biologically active compounds. Herein, we report their operationally simple synthesis through an iron-catalyzed difunctionalization of alkenes. A wide array of alkene substrates are tolerated, including complex drug-like molecules and a tripeptide. Facile derivatizations of the azidoamine group demonstrate the versatility of this masked diamine motif in chemoselective, orthogonal transformations. Applications of the methodology in the concise synthesis of RO 20-1724 as well as in the formal total syntheses of both (±)-hamacanthin B and (±)-quinagolide further demonstrate the broad synthetic potential of this highly functional-group-tolerant reaction.

Design and Scalable Synthesis of N-Alkylhydroxylamine Reagents for the Direct Iron-Catalyzed Installation of Medicinally Relevant Amines*.

Secondary and tertiary alkylamines are privileged substance classes that are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of ten novel hydroxylamine-derived aminating reagents were designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The method has excellent functional group tolerance and a broad scope of alkenes was converted to the corresponding products, including several drug-like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.

Iron-Catalyzed Ring-Closing C-O/C-O Metathesis of Aliphatic Ethers.

Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring-closing reactions. Herein, we report an iron-catalyzed ring-closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.

Rapid Asymmetric Synthesis of Disubstituted Allenes by Coupling of Flow-Generated Diazo Compounds and Propargylated Amines.

We report herein the asymmetric coupling of flow-generated unstabilized diazo compounds and propargylated amine derivatives, using a new pyridinebis(imidazoline) ligand, a copper catalyst and base. The reaction proceeds rapidly, generating chiral allenes in 10-20 minutes with high enantioselectivity (89-98 % de/ee), moderate yields and a wide functional group tolerance.

A Catalog of Regulatory Sequences for Trait Gene for the Genome Editing of Wheat.

Wheat has been cultivated for 10000 years and ever since the origin of hexaploid wheat it has been exempt from natural selection. Instead, it was under the constant selective pressure of human agriculture from harvest to sowing during every year, producing a vast array of varieties. Wheat has been adopted globally, accumulating variation for genes involved in yield traits, environmental adaptation and resistance. However, one small but important part of the wheat genome has hardly changed: the regulatory regions of both the x- and y-type high molecular weight glutenin subunit (HMW-GS) genes, which are alone responsible for approximately 12% of the grain protein content. The phylogeny of the HMW-GS regulatory regions of the Triticeae demonstrates that a genetic bottleneck may have led to its decreased diversity during domestication and the subsequent cultivation. It has also highlighted the fact that the wild relatives of wheat may offer an unexploited genetic resource for the regulatory region of these genes. Significant research efforts have been made in the public sector and by international agencies, using wild crosses to exploit the available genetic variation, and as a result synthetic hexaploids are now being utilized by a number of breeding companies. However, a newly emerging tool of genome editing provides significantly improved efficiency in exploiting the natural variation in HMW-GS genes and incorporating this into elite cultivars and breeding lines. Recent advancement in the understanding of the regulation of these genes underlines the needs for an overview of the regulatory elements for genome editing purposes.

Multiple elements controlling the expression of wheat high molecular weight glutenin paralogs.

Analysis of gene expression data generated by high-throughput microarray transcript profiling experiments coupled with cis-regulatory elements enrichment study and cluster analysis can be used to define modular gene programs and regulatory networks. Unfortunately, the high molecular weight glutenin subunits of wheat (Triticum aestivum) are more similar than microarray data alone would allow to distinguish between the three homoeologous gene pairs. However, combining complementary DNA (cDNA) expression libraries with microarray data, a co-expressional network was built that highlighted the hidden differences between these highly similar genes. Duplex clusters of cis-regulatory elements were used to focus the co-expressional network of transcription factors to the putative regulatory network of Glu-1 genes. The focused network helped to identify several transcriptional gene programs in the endosperm. Many of these programs demonstrated a conserved temporal pattern across the studied genotypes; however, few others showed variance. Based on this network, transient gene expression assays were performed with mutated promoters to inspect the control of tissue specificity. Results indicated that the interactions of the ABRE│CBF cluster with distal promoter regions may have a dual role in regulation by both recruiting the transcription complex as well as suppressing it in non-endosperm tissue. A putative model of regulation is discussed.

A census of nuclear cyanobacterial recruits in the plant kingdom.

The plastids and mitochondria of the eukaryotic cell are of endosymbiotic origin. These events occurred ~2 billion years ago and produced significant changes in the genomes of the host and the endosymbiont. Previous studies demonstrated that the invasion of land affected plastids and mitochondria differently and that the paths of mitochondrial integration differed between animals and plants. Other studies examined the reasons why a set of proteins remained encoded in the organelles and were not transferred to the nuclear genome. However, our understanding of the functional relations of the transferred genes is insufficient. In this paper, we report a high-throughput phylogenetic analysis to identify genes of cyanobacterial origin for plants of different levels of complexity: Arabidopsis thaliana, Chlamydomonas reinhardtii, Physcomitrella patens, Populus trichocarpa, Selaginella moellendorffii, Sorghum bicolor, Oryza sativa, and Ostreococcus tauri. Thus, a census of cyanobacterial gene recruits and a study of their function are presented to better understand the functional aspects of plastid symbiogenesis. From algae to angiosperms, the GO terms demonstrated a gradual expansion over functionally related genes in the nuclear genome, beginning with genes related to thylakoids and photosynthesis, followed by genes involved in metabolism, and finally with regulation-related genes, primarily in angiosperms. The results demonstrate that DNA is supplied to the nuclear genome on a permanent basis with no regard to function, and only what is needed is kept, which thereby expands on the GO space along the related genes.

Role of conserved non-coding regulatory elements in LMW glutenin gene expression.

Transcriptional regulation of LMW glutenin genes were investigated in-silico, using publicly available gene sequences and expression data. Genes were grouped into different LMW glutenin types and their promoter profiles were determined using cis-acting regulatory elements databases and published results. The various cis-acting elements belong to some conserved non-coding regulatory regions (CREs) and might act in two different ways. There are elements, such as GCN4 motifs found in the long endosperm box that could serve as key factors in tissue-specific expression. Some other elements, such as the AACA/TA motifs or the individual prolamin box variants, might modulate the level of expression. Based on the promoter sequences and expression characteristic LMW glutenin genes might be transcribed following two different mechanisms. Most of the s- and i-type genes show a continuously increasing expression pattern. The m-type genes, however, demonstrate normal distribution in their expression profiles. Differences observed in their expression could be related to the differences found in their promoter sequences. Polymorphisms in the number and combination of cis-acting elements in their promoter regions can be of crucial importance in the diverse levels of production of single LMW glutenin gene types.