Tissue-specific usage of transposable element-derived promoters in mouse development

BACKGROUND: Transposable elements (TEs) are a significant component of eukaryotic genomes and play essential roles in genome evolution. Mounting evidence indicates that TEs are highly transcribed in early embryo development and contribute to distinct biological functions and tissue morphology. RESULTS: We examine the epigenetic dynamics of mouse TEs during the development of five tissues: intestine, liver, lung, stomach, and kidney. We found that TEs are associated with over 20% of open chromatin regions during development. Close to half of these accessible TEs are only activated in a single tissue and a specific developmental stage. Most accessible TEs are rodent-specific. Across these five tissues, 453 accessible TEs are found to create the transcription start sites of downstream genes in mouse, including 117 protein-coding genes and 144 lincRNA genes, 93.7% of which are mouse-specific. Species-specific TE-derived transcription start sites are found to drive the expression of tissue-specific genes and change their tissue-specific expression patterns during evolution. CONCLUSION: Our results suggest that TE insertions increase the regulatory potential of the genome, and some TEs have been domesticated to become a crucial component of gene and regulate tissue-specific expression during mouse tissue development

Common DNA methylation dynamics in endometriod adenocarcinoma and glioblastoma suggest universal epigenomic alterations in tumorigenesis

Trends in altered DNA methylation have been defined across human cancers, revealing global loss of methylation (hypomethylation) and focal gain of methylation (hypermethylation) as frequent cancer hallmarks. Although many cancers share these trends, little is known about the specific differences in DNA methylation changes across cancer types, particularly outside of promoters. Here, we present a comprehensive comparison of DNA methylation changes between two distinct cancers, endometrioid adenocarcinoma (EAC) and glioblastoma multiforme (GBM), to elucidate common rules of methylation dysregulation and changes unique to cancers derived from specific cells. Both cancers exhibit significant changes in methylation over regulatory elements. Notably, hypermethylated enhancers within EAC samples contain several transcription factor binding site clusters with enriched disease ontology terms highlighting uterine function, while hypermethylated enhancers in GBM are found to overlap active enhancer marks in adult brain. These findings suggest that loss of original cellular identity may be a shared step in tumorigenesis

AIAP: A quality control and integrative analysis package to improve ATAC-seq data analysis

Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate analysis. Several tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data; however, key quality control (QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics for ATAC-seq data, including reads under peak ratio (RUPr), background (BG), promoter enrichment (ProEn), subsampling enrichment (SubEn), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package (AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity (20%-60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and it can be executed by one command line to generate a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed qATACViewer for the user-friendly interaction with the QC report. The software, source code, and documentation of AIAP are freely available at https://github.com/Zhang-lab/ATAC-seq_QC_analysis

The transcription factor Bach2 negatively regulates murine natural killer cell maturation and function

BTB domain And CNC Homolog 2 (Bach2) is a transcription repressor that actively participates in T and B lymphocyte development, but it is unknown if Bach2 is also involved in the development of innate immune cells, such as natural killer (NK) cells. Here, we followed the expression of Bach2 during murine NK cell development, finding that it peaked in immature CD2

Synthesis and Properties of Macrocyclic Butanoic Acid Conjugates as a Promising Delivery Formulation for the Nutrition of Colon

Butanoic acid plays a significant role in the maintenance of mucosal health and is the preferred energy substrate for the cells in the colon. Here, butanoic acid was selectively conjugated to the secondary hydroxyl group of β-cyclodextrin through ester bond using sodium hydride as the deprotonation reagent. The preliminary release behaviors of butanoic acid in rat gastrointestinal tract contents were investigated at 37°C within 12 h. In the contents of stomach, the conjugates did seldom release butanoic acid, released butanoic acid only 5.8% in the contents of small intestine, and released butanoic acid significantly up to 38.4% in the contents of colon. These results indicate that the conjugate activation took place site specifically in the rat colonic contents, via the biodegradation by glycosidases and hydrolases in the colon. Therefore, the β-cyclodextrin conjugates of butanoic acid may be of value as an orally administered colon-specific formulation for the nutrition of colon

Evaluation of functionality for serine and threonine phosphorylation with different evolutionary ages in human and mouse

Abstract Background Rapid evolution of phosphorylation sites could provide raw materials of natural selection to fit the environment by rewiring the regulation of signal pathways. However, a large part of phosphorylation sites was suggested to be non-functional. Although the new-arising phosphorylation sites with little functional implications prevailed in fungi, the evolutionary performance of vertebrate phosphorylation sites remained elusive. Results In this study, we evaluated the functionality of human and mouse phosphorylation sites by dividing them into old, median and young age groups based on the phylogeny of vertebrates. We found the sites in the old group were more likely to be functional and involved in signaling pathways than those in the young group. A smaller proportion of sites in the young group originated from aspartate/glutamate, which could restore the ancestral functions. In addition, both the phosphorylation level and breadth was increased with the evolutionary age. Similar to cases in fungi, these results implied that the newly emerged phosphorylation sites in vertebrates were also more likely to be non-functional, especially for serine and threonine phosphorylation in disordered regions. Conclusions This study provided not only insights into the dynamics of phosphorylation evolution in vertebrates, but also new clues to identify the functional phosphorylation sites from massive noisy data

Polyploidization Genetic Mechanism of Sugarcane Genome

The sugarcane genome polyploidization can reduce the pressure of gene evolution selection, promote the fixation of fine traits, and increase the biomass and economic value of sugarcane. This paper mainly introduced the origin of the sugarcane genome, the chromosome composition, the research progress of polyploidization genetic mechanism, in the hope of providing theoretical reference for sugarcane polyploidization breeding

Probing Surface Information of Alloy by Time of Flight-Secondary Ion Mass Spectrometer

In recent years, time of flight-secondary ion mass spectrometer (ToF-SIMS) has been widely employed to acquire surface information of materials. Here, we investigated the alloy surface by combining the mass spectra and 2D mapping images of ToF-SIMS. We found by surprise that these two results seem to be inconsistent with each other. Therefore, other surface characteristic tools such as SEM-EDS were further used to provide additional supports. The results indicated that such differences may originate from the variance of secondary ion yields, which might be affected by crystal orientation

Solid-State Hydrogen Storage Properties of Ti–V–Nb–Cr High-Entropy Alloys and the Associated Effects of Transitional Metals (M = Mn, Fe, Ni)

Recently, high-entropy alloys (HEAs) designed by the concepts of unique entropy-stabilized mechanisms, started to attract widespread interests for their hydrogen storage properties. HEAs with body-centered cubic (BCC) structures present a high potential for hydrogen storage due to the high hydrogen-to-metal ratio (up to H/M = 2) and vastness of compositions. Although many studies reported rapid absorption kinetics, the investigation of hydrogen desorption is missing, especially in BCC HEAs. We have investigated the crystal structure, microstructure and hydrogen storage performance of a series of HEAs in the Ti–V–Nb–Cr system. Three types of TiVCrNb HEAs (Ti4V3NbCr2, Ti3V3Nb2Cr2, Ti2V3Nb3Cr2) with close atomic radii and different valence electron concentrations (VECs) were designed with single BCC phase by CALPHAD method. The three alloys with fast hydrogen absorption kinetics reach the H/M ratio up to 2. Particularly, Ti4V3NbCr2 alloy shows the hydrogen storage capacity of 3.7 wt%, higher than other HEAs ever reported. The dehydrogenation activation energy of HEAs’ hydride has been proved to decrease with decreasing VEC, which may be due to the weakening of alloy atom and H atom. Moreover, Ti4V3NbCr2M (M = Mn, Fe, Ni) alloys were also synthesized to destabilize hydrides. The addition of Mn, Fe and Ni lead to precipitation of Laves phase, however, the kinetics did not improve further because of their own excellent hydrogen absorption. With increasing the content of Laves phase, there appear more pathways for hydrogen desorption so that the hydrides are more easily dissociated, which may provide new insights into how to achieve hydrogen desorption in BCC HEAs at room temperature