Interfacial water confers transcription factors with dinucleotide specificity.

Transcription factors (TFs) recognize specific bases within their DNA-binding motifs, with each base contributing nearly independently to total binding energy. However, the energetic contributions of particular dinucleotides can deviate strongly from the additive approximation, indicating that some TFs can specifically recognize DNA dinucleotides. Here we solved high-resolution (<1 Å) structures of MYF5 and BARHL2 bound to DNAs containing sets of dinucleotides that have different affinities to the proteins.

A novel interpretable deep learning-based computational framework designed synthetic enhancers with broad cross-species activity.

Enhancers play a critical role in dynamically regulating spatial-temporal gene expression and establishing cell identity, underscoring the significance of designing them with specific properties for applications in biosynthetic engineering and gene therapy. Despite numerous high-throughput methods facilitating genome-wide enhancer identification, deciphering the sequence determinants of their activity remains challenging. Here, we present the DREAM (DNA cis-Regulatory Elements with controllable Activity design platforM) framework, a novel deep learning-based approach for synthetic enhancer design.

A Spatiotemporal Transcriptome Reveals Stalk Development in Pearl Millet.

Pearl millet is a major cereal crop that feeds more than 90 million people worldwide in arid and semi-arid regions. The stalk phenotypes of Poaceous grasses are critical for their productivity and stress tolerance; however, the molecular mechanisms governing stalk development in pearl millet remain to be deciphered. In this study, we spatiotemporally measured 19 transcriptomes for stalk internodes of four different early developmental stages.

Sea-ATI unravels novel vocabularies of plant active cistrome.

The cistrome consists of all cis-acting regulatory elements recognized by transcription factors (TFs). However, only a portion of the cistrome is active for TF binding in a specific tissue. Resolving the active cistrome in plants remains challenging.

Milletdb: a multi-omics database to accelerate the research of functional genomics and molecular breeding of millets.

Millets are a class of nutrient-rich coarse cereals with high resistance to abiotic stress; thus, they guarantee food security for people living in areas with extreme climatic conditions and provide stress-related genetic resources for other crops. However, no platform is available to provide a comprehensive and systematic multi-omics analysis for millets, which seriously hinders the mining of stress-related genes and the molecular breeding of millets. Here, a free, web-accessible, user-friendly millets multi-omics database platform (Milletdb, http://milletdb.

Ectopic Expression of Promotes Secondary Cell Wall Thickening and Flavonoid Accumulation in .

Secondary cell wall (SCW) thickening has a significant effect on the growth and development of plants, as well as in the resistance to various biotic and abiotic stresses. Lignin accounts for the strength of SCW. It is synthesized through the phenylpropanoid pathway that also leads to flavonoid synthesis.

Sequence determinants of human gene regulatory elements.

DNA can determine where and when genes are expressed, but the full set of sequence determinants that control gene expression is unknown. Here, we measured the transcriptional activity of DNA sequences that represent an ~100 times larger sequence space than the human genome using massively parallel reporter assays (MPRAs). Machine learning models revealed that transcription factors (TFs) generally act in an additive manner with weak grammar and that most enhancers increase expression from a promoter by a mechanism that does not appear to involve specific TF-TF interactions.

Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences.

RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-throughput RNA-SELEX (HTR-SELEX).

Nucleosome-bound SOX2 and SOX11 structures elucidate pioneer factor function.

'Pioneer' transcription factors are required for stem-cell pluripotency, cell differentiation and cell reprogramming. Pioneer factors can bind nucleosomal DNA to enable gene expression from regions of the genome with closed chromatin. SOX2 is a prominent pioneer factor that is essential for pluripotency and self-renewal of embryonic stem cells.

The interaction landscape between transcription factors and the nucleosome.

Nucleosomes cover most of the genome and are thought to be displaced by transcription factors in regions that direct gene expression. However, the modes of interaction between transcription factors and nucleosomal DNA remain largely unknown. Here we systematically explore interactions between the nucleosome and 220 transcription factors representing diverse structural families.

A protein activity assay to measure global transcription factor activity reveals determinants of chromatin accessibility.

No existing method to characterize transcription factor (TF) binding to DNA allows genome-wide measurement of all TF-binding activity in cells. Here we present a massively parallel protein activity assay, active TF identification (ATI), that measures the DNA-binding activity of all TFs in cell or tissue extracts. ATI is based on electrophoretic separation of protein-bound DNA sequences from a highly complex DNA library and subsequent mass-spectrometric identification of the DNA-bound proteins.

Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima.

Most transcription factors (TFs) can bind to a population of sequences closely related to a single optimal site. However, some TFs can bind to two distinct sequences that represent two local optima in the Gibbs free energy of binding (ΔG). To determine the molecular mechanism behind this effect, we solved the structures of human HOXB13 and CDX2 bound to their two optimal DNA sequences, CAATAAA and TCGTAAA.

Effects of magnesium ions and water molecules on the structure of amorphous calcium carbonate: a molecular dynamics study.

Molecular dynamics simulations were conducted to elucidate the effects of Mg(2+) and H2O additives on the structure of amorphous calcium carbonate (ACC). New potential parameters for Mg(2+) ions were developed. The distribution function of the angle formed by three nearest-neighbor atoms was introduced to analyze the short-range local structure of ACC.

Tuning the stability of CaCO3 crystals with magnesium ions for the formation of aragonite thin films on organic polymer templates.

Thin-film growth of aragonite CaCO3 on annealed poly(vinyl alcohol) (PVA) matrices is induced by adding Mg(2+) into a supersaturated solution of CaCO3. Both the growth rate and surface morphology of the aragonite thin films depend upon the concentration of Mg(2+) in the mineralization solution. In the absence of PVA matrices, no thin films are formed, despite the presence of Mg(2+).

Subcellular localization of N-deoxyribosyltransferase in Lactobacillus fermentum: cell surface association of an intracellular nucleotide metabolic enzyme.

N-deoxyribosyltransferases are essential enzymes in the nucleotide salvage pathway of lactobacilli. They catalyze the exchange between the purine or pyrimidine bases of 2'-deoxyribonucleosides and free pyrimidine or purine bases. In general, N-deoxyribosyltransferases are referred to as cytoplasmic enzymes, although there is no experimental evidence for this subcellular localization.

Molecular approaches to understand biomineralization of shell nacreous layer.

The nacreous layer of molluskan shells, which consists of highly oriented aragonitic crystals and an organic matrix (including chitin and proteins), is a product of biomineralization. This paper briefly introduces the recent research advances on nacre biomineralization of shells from bivalves and gastropods, which mainly focus on analysis of the micro- and nano-structure and components of shell nacreous layers, and investigations of the characteristics and functions of matrix proteins from nacre. Matrix proteins not only participate in construction of the organic nacre framework, but also control the nucleation and growth of aragonitic crystals, as well as determine the polymorph specificity of calcium carbonate in nacre.

Cloning, characterization and immunolocalization of two subunits of calcineurin from pearl oyster (Pinctada fucata).

Calcineurin (CN), consisting of catalytic subunit (CN A) and regulatory subunit (CN B), is a multifunctional protein involved in many important physiological processes. Here, we cloned two subunits of CN (Pf-CN A and Pf-CN B) from pearl oyster Pinctada fucata and reported, for the first time, its expression patterns in the developmental stages, its enzymatic activity and immunolocalization in various tissues of adult pearl oyster. The Pf-CN A was extensively localized in all the tested tissues including mantle, gonad, digestive gland, gills, adductor muscle, and foot with strong signals detected in gonad, gills, foot, and mantle.

Cloning and characterization of Prisilkin-39, a novel matrix protein serving a dual role in the prismatic layer formation from the oyster Pinctada fucata.

Molluscs form their shells out of CaCO(3) and a matrix of biomacromolecules. Understanding the role of matrices may shed some light on the mechanism of biomineralization. Here, a 1401-bp full-length cDNA sequence encoding a novel matrix protein was cloned from the mantle of the bivalve oyster, Pinctada fucata.