Defect-enriched (H2PO4-, Cr3+)-α-Fe2O3/ß-In2S3 composites for visible light degradation of 4-nitrophenol.

In this work, the high-activity (H2PO4-, Cr3+)-α-Fe2O3 (PCF) with abundant oxygen vacancies (OVs) and the high specific area was obtained by co-adding H2PO4- and Cr3+. Defect-enriched PCF/ß-In2S3 composites were prepared by low-temperature hydrothermal processes. The prepared composites exhibited improved photocatalytic degradation of 4-nitrophenol under visible light irradiation.The SO bond between PCF and ß-In2S3 promoted the formation of tight heterojunction composites and increased the OVs concentration. Under the synergistic effect of photo-Fenton, defects, and heterojunction, the PCF/ß-In2S3 composites effectively promoted the separation of photogenerated carriers and accelerated the production of active substances (•OH, •O2-, 1O2, and h+), leading to the improvement of photocatalytic-Fenton degradation performance. This work provided a new strategy for the preparation of highly efficient photocatalysts.

Mapping nucleolus-associated chromatin interactions using nucleolus Hi-C reveals pattern of heterochromatin interactions.

As the largest substructures in the nucleus, nucleoli are the sites of ribosome biogenesis. Increasing evidence indicates that nucleoli play a key role in the organization of 3D genome architecture, but systematic studies of nucleolus-associated chromatin interactions are lacking. Here, we developed a nucleolus Hi-C (nHi-C) experimental technique to enrich nucleolus-associated chromatin interactions. Using the nHi-C experiment, we identify 264 high-confidence nucleolus-associated domains (hNADs) that form strong heterochromatin interactions associated with the nucleolus and consist of 24% of the whole genome in HeLa cells. Based on the global hNAD inter-chromosomal interactions, we find five nucleolar organizer region (NOR)-bearing chromosomes formed into two clusters that show different interaction patterns, which is concordant with their epigenetic states and gene expression levels. hNADs can be divided into three groups that display distinct cis/trans interaction signals, interaction frequencies associated with nucleoli, distance from the centromeres, and overlap percentage with lamina-associated domains (LADs). Nucleolus disassembly caused by Actinomycin D (ActD) significantly decreases the strength of hNADs and affects compartment/TAD strength genome-wide. In summary, our results provide a global view of heterochromatin interactions organized around nucleoli and demonstrate that nucleoli act as an inactive inter-chromosomal hub to shape both compartments and TADs.

Chromatin accessibility shapes meiotic recombination in mouse primordial germ cells through assisting double-strand breaks and loop formation.

Meiotic recombination is a driver of evolution, and aberrant recombination is a major contributor to aneuploidy in mammals. Mechanism of recombination remains elusive yet. Here, we present a computational analysis to explore recombination-related dynamics of chromatin accessibility in mouse primordial germ cells (PGCs). Our data reveals that: (1) recombination hotspots which get accessible at meiosis-specific DNase I-hypersensitive sites (DHSs) only when PGCs enter meiosis are located preferentially in intronic and distal intergenic regions; (2) stable DHSs maintained stably across PGC differentiation are enriched by CTCF motifs and CTCF binding and mediate chromatin loop formation; (3) compared with the specific DHSs aroused at meiotic stage, stable DHSs are largely encoded in DNA sequence and also enriched by epigenetic marks; (4) PRDM9 is likely to target nucleosome-occupied hotspot regions and remodels local chromatin structure to make them accessible for recombination machinery; and (5) cells undergoing meiotic recombination are deficient in TAD structure and chromatin loop arrays are organized regularly along the axis formed between homologous chromosomes. Taken together, by analyzing DHS-related DNA features, epigenetic marks and 3D genome structure, we revealed some specific roles of chromatin accessibility in recombination, which would expand our understanding of recombination mechanism.

CTCF organizes inter-A compartment interactions through RYBP-dependent phase separation.

Chromatin is spatially organized into three-dimensional structures at different levels including A/B compartments, topologically associating domains and loops. The canonical CTCF-mediated loop extrusion model can explain the formation of loops. However, the organization mechanisms underlying long-range chromatin interactions such as interactions between A-A compartments are still poorly understood. Here we show that different from the canonical loop extrusion model, RYBP-mediated phase separation of CTCF organizes inter-A compartment interactions. Based on this model, we designed and verified an induced CTCF phase separation system in embryonic stem cells (ESCs), which facilitated inter-A compartment interactions, improved self-renewal of ESCs and inhibited their differentiation toward neural progenitor cells. These findings support a novel and non-canonical role of CTCF in organizing long-range chromatin interactions via phase separation.

Fabrication of CdS/Ti3C2/g-C3N4NS Z-scheme composites with enhanced visible light-driven photocatalytic activity.

The Ti3C2 and g-C3N4NS were obtained first, and the CdS/Ti3C2/g-C3N4NS Z-scheme composites were prepared via a facile hydrothermal synthesis, and their photocatalytic properties were investigated. The g-C3N4NS with a high surface area displayed higher adsorption and degradation capacity. Compared with Ti3C2/g-C3N4NS and CdS, the visible light photocatalytic activity of CdS/Ti3C2/g-C3N4NS composites was improved. The as-synthesized CTN-4:1 composite exhibited outstanding photocatalytic performance for degradation of orange II, approximately 3.2 and 10.7 times higher than that of Ti3C2/g-C3N4NS and CdS, respectively. The fabrication of CdS/Ti3C2/g-C3N4NS Z-scheme heterostructure using Ti3C2 as electron transfer medium improved the separation ability of the photoinduced e--h+ pairs, thereby leading to the improvement of visible light-driven photocatalytic activity. This finding provides new insights into the construction of high efficiency Z-scheme heterostructure photocatalyst.

Using Open Chromatin Enrichment and Network Hi-C (OCEAN-C) to Identify Open Chromatin Interactions.

The open chromatin enrichment and network Hi-C (OCEAN-C) was developed not only for identifying large-scale chromatin structures, including topologically associated domains (TADs) and A/B compartments, but also for globally mapping hubs of open chromatin interactions (HOCIs) and their interaction networks independent of antibody and bait-sequences.

Phase separation of OCT4 controls TAD reorganization to promote cell fate transitions.

Topological-associated domains (TADs) are thought to be relatively stable across cell types, although some TAD reorganization has been observed during cellular differentiation. However, little is known about the mechanisms through which TAD reorganization affects cell fate or how master transcription factors affect TAD structures during cell fate transitions. Here, we show extensive TAD reorganization during somatic cell reprogramming, which is correlated with gene transcription and changes in cellular identity. Manipulating TAD reorganization promotes reprogramming, and the dynamics of concentrated chromatin loops in OCT4 phase separated condensates contribute to TAD reorganization. Disrupting OCT4 phase separation attenuates TAD reorganization and reprogramming, which can be rescued by fusing an intrinsically disordered region (IDR) to OCT4. We developed an approach termed TAD reorganization-based multiomics analysis (TADMAN), which identified reprogramming regulators. Together, these findings elucidate a role and mechanism of TAD reorganization, regulated by OCT4 phase separation, in cellular reprogramming.

Senescence-activated enhancer landscape orchestrates the senescence-associated secretory phenotype in murine fibroblasts.

The three-dimensional configuration of the chromatin architecture is known to be crucial for alterations in the transcriptional network; however, the underlying mechanisms of epigenetic control of senescence-related gene expression by modulating the chromatin architecture remain unknown. Here, we demonstrate frequent chromosomal compartment switching during mouse embryonic fibroblasts (MEFs) replicative senescence as characterized by senescence-inactivated (SIAEs) and -activated enhancers (SAEs) in topologically associated domains (TADs). Mechanistically, SAEs are closely correlated with senescence-associated secretory phenotype (SASP) genes, which are a key transcriptional feature of an aging microenvironment that contributes to tumor progression, aging acceleration, and immunoinflammatory responses. Moreover, SAEs can positively regulate robust changes in SASP expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is capable of enhancing SAE activity, which accelerates the emergence of SAEs flanking SASPs and the secretion of downstream factors, contributing to the progression of senescence. Our results provide novel insight into the TAD-related control of SASP gene expression by revealing hierarchical roles of the chromatin architecture, transcription factors, and enhancer activity in the regulation of cellular senescence.

tagHi-C Reveals 3D Chromatin Architecture Dynamics during Mouse Hematopoiesis.

Spatiotemporal chromatin reorganization during hematopoietic differentiation has not been comprehensively characterized, mainly because of the large numbers of starting cells required for current chromatin conformation capture approaches. Here, we introduce a low-input tagmentation-based Hi-C (tagHi-C) method to capture the chromatin structures of hundreds of cells. Using tagHi-C, we are able to map the spatiotemporal dynamics of chromatin structure in ten primary hematopoietic stem, progenitor, and differentiated cell populations from mouse bone marrow. Our results reveal that changes in compartment dynamics and the Rabl configuration occur during hematopoietic cell differentiation. We identify gene-body-associating domains (GADs) as general structures for highly expressed genes. Moreover, we extend the body of knowledge regarding genes influenced by genome-wide association study (GWAS) loci through spatial chromatin looping. Our study provides the tagHi-C method for studying the three-dimensional (3D) genome of a small number of cells and maps the comprehensive 3D chromatin landscape of bone marrow hematopoietic cells.

PCGF6 regulates stem cell pluripotency as a transcription activator via super-enhancer dependent chromatin interactions.

Polycomb group (PcG) ring finger protein 6 (PCGF6), though known as a member of the transcription-repressing complexes, PcG, also has activation function in regulating pluripotency gene expression. However, the mechanism underlying the activation function of PCGF6 is poorly understood. Here, we found that PCGF6 co-localizes to gene activation regions along with pluripotency factors such as OCT4. In addition, PCGF6 was recruited to a subset of the super-enhancer (SE) regions upstream of cell cycle-associated genes by OCT4, and increased their expression. By combining with promoter capture Hi-C data, we found that PCGF6 activates cell cycle genes by regulating SE-promoter interactions via 3D chromatin. Our findings highlight a novel mechanism of PcG protein in regulating pluripotency, and provide a research basis for the therapeutic application of pluripotent stem cells.

OCEAN-C: mapping hubs of open chromatin interactions across the genome reveals gene regulatory networks.

We develop a method called open chromatin enrichment and network Hi-C (OCEAN-C) for antibody-independent mapping of global open chromatin interactions. By integrating FAIRE-seq and Hi-C, OCEAN-C detects open chromatin interactions enriched by active cis-regulatory elements. We identify more than 10,000 hubs of open chromatin interactions (HOCIs) in human cells, which are mainly active promoters and enhancers bound by many DNA-binding proteins and form interaction networks crucial for gene transcription. In addition to identifying large-scale topological structures, including topologically associated domains and A/B compartments, OCEAN-C can detect HOCI-mediated chromatin interactions that are strongly associated with gene expression, super-enhancers, and broad H3K4me3 domains.

3D genome of multiple myeloma reveals spatial genome disorganization associated with copy number variations.

The Hi-C method is widely used to study the functional roles of the three-dimensional (3D) architecture of genomes. Here, we integrate Hi-C, whole-genome sequencing (WGS) and RNA-seq to study the 3D genome architecture of multiple myeloma (MM) and how it associates with genomic variation and gene expression. Our results show that Hi-C interaction matrices are biased by copy number variations (CNVs) and can be used to detect CNVs. Also, combining Hi-C and WGS data can improve the detection of translocations. We find that CNV breakpoints significantly overlap with topologically associating domain (TAD) boundaries. Compared to normal B cells, the numbers of TADs increases by 25% in MM, the average size of TADs is smaller, and about 20% of genomic regions switch their chromatin A/B compartment types. In summary, we report a 3D genome interaction map of aneuploid MM cells and reveal the relationship among CNVs, translocations, 3D genome reorganization, and gene expression regulation.

Isocitrate lyase is required for urediniospore germination of Puccinia striiformis f. sp. tritici.

The PstICL1 gene, which encodes isocitrate lyase, a key enzyme in the glyoxylate cycle, was cloned and characterized in the biotrophic wheat pathogen Puccinia striiformis f. sp. tritici (Pst). Expression analyses of PstICL1 exhibited high levels of transcripts in ungerminated urediniospores, which showed low isocitrate lyase enzyme activity. In planta, PstICL1 expression was continuously down-regulated upon germination. During the later stages of the infection of wheat, the level of PstICL1 expression was extremely low. The function of PstICL1 was identified via mutant complementation. The expression of PstICL1 in Saccharomyces cerevisiae can complement the defects of the △ICL mutant. Using 3-nitropropionate, we observed that inactivation of isocitrate lyase greatly reduced the germination rate of urediniospores, indicating that PstICL1 plays a key role during Pst germination. Furthermore, analysis of lipid bodies revealed that lipid components continuously enter the germ tube from the urediniospore cell during germ tube elongation. Moreover, during this period, the lipid contents continuously decreased, and the total carbohydrates markedly increased, demonstrating that the lipids are being converted into carbohydrates. These results suggest that PstICL1 is required for Pst germination.