Biology subjects

Zhang, C.

Publications and source records attributed to Zhang, C..

At least 685 records · Page 38Linked to original sources

bioRxiv2022

Spatial chromatin accessibility sequencing resolves next-generation genome architecture

As the genome is organized into a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, most epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the horizontal dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to resolve the genome conformation by capturing the epigenetic information in single-molecular resolution while simultaneously resolving the genome conformation. Using SCA-seq, we are able to examine the spatial interaction of chromatin accessibility (e.g. enhancer-promoter contacts), CpG island methylation, and spatial insulating functions of the CCCTC-binding factor. We demonstrate that SCA-seq paves the way to explore the mechanism of epigenetic interactions and extends our knowledge in 3D packaging of DNA in the nucleus.

genomics↗

bioRxiv2022

Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via epigenetic regulation of key regenerative pathways

Current clinical treatment for neurodegenerative diseases and neural injuries falls short of success, and one primary reason is that neurons in the mammalian central nervous system (CNS) lose their regeneration ability as they mature. Previous studies indicated that the regeneration ability of neurons is governed by complex signaling networks involving many genes. Therefore, here we investigated the roles of Ezh2, a histone methyltransferase, in regulation of mammalian axon regeneration at the epigenetic level. We found that Ezh2 level was gradually downregulated in the mouse nervous system during maturation but significantly upregulated in mature sensory neurons during spontaneous axon regeneration in the peripheral nerve system (PNS), suggesting its role in supporting axon regeneration. Indeed, Ezh2 loss-of-function in sensory neurons impaired PNS axon regeneration in vitro and in vivo. In contrast, overexpression of Ezh2 in retinal ganglion cells in the CNS induced optic nerve regeneration after optic nerve injury in both methyltransferase-dependent and -independent manners. Mechanistic exploration with multiomics sequencing, together with functional analyses, revealed that Ezh2 supported axon regeneration by systematically silencing the transcription of genes regulating synaptic function and axon regeneration inhibitory signaling, while broadly activating factors promoting axon regeneration. Our study not only reveals that Ezh2 coordinates axon regeneration via epigenetically regulating multiple key regenerative pathways, but also suggests that modulating chromatin accessibility is a promising strategy to promote CNS axon regeneration.

neuroscience↗

bioRxiv2022

Phertilizer: growing a clonal tree from ultra-low coverage single-cell DNA sequencing data of tumors

Emerging ultra-low coverage single-cell DNA sequencing (scDNA-seq) technologies have enabled high resolution evolutionary studies of copy number aberrations (CNAs) within tumors. While these sequencing technologies are well suited for identifying CNAs due to the uniformity of sequencing coverage, the sparsity of coverage poses challenges for the study of single-nucleotide variants (SNVs). In order to maximize the utility of increasingly available ultra-low coverage scDNA-seq data and obtain a comprehensive understanding of tumor evolution, it is important to also analyze the evolution of SNVs from the same set of tumor cells. We present PO_SCPLOWHERTILIZERC_SCPLOW, a method to infer a clonal tree from ultra-low coverage scDNA-seq data of a tumor. Based on a probabilistic model, our method recursively partitions the data by identifying key evolutionary events in the history of the tumor. We demonstrate the performance of PO_SCPLOWHERTILIZERC_SCPLOW on simulated data as well as on two real datasets, finding that PO_SCPLOWHERTILIZERC_SCPLOW effectively utilizes the copynumber signal inherent in the data to more accurately uncover clonal structure and genotypes compared to previous methods. Availabilityhttps://github.com/elkebir-group/phertilizer

bioinformatics↗

bioRxiv2022

Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish gastrulation

Chemical signaling is the primary means by which cells communicate in the embryo. The underlying principle refers to a group of ligand-producing cells and a group of cells that respond to this signal because they express the appropriate receptors. In the zebrafish embryo, Wnt5b binds to the receptor Ror2 to trigger the Wnt/Planar Cell Polarity (Wnt/PCP) signaling pathway to regulate tissue polarity and cell migration. However, it is still unclear how this lipophilic ligand is transported from the source cells through the aqueous extracellular space to the target tissue. Here we show that Wnt5b, together with Ror2, is loaded on long protrusions. The active Wnt5b/Ror2 complexes are handed over from these cytonemes to the receiving cell to trigger Wnt/PCP signaling, regardless of whether the cell expresses functional receptors. On the tissue level, we show that cytoneme-dependent spreading of active Wnt5b/Ror2 affects convergence and extension in the zebrafish gastrula.

developmental biology↗

bioRxiv2022

Cancer-associated fibroblast-derived ROR2 induces WNT/PCP activation and polarized migration in receiving gastric cancer cells.

Bone marrow-derived mesenchymal stem cells and cancer-associated fibroblasts in the tumor-stromal environment have been linked to cancer progression in many studies. These fibroblasts provide signaling factors to the tumor cells that promote proliferation, survival, invasion, and metastasis. One signaling pathway influencing tumor cell behavior is the WNT/Planar Cell Polarity (PCP) signaling in gastric cancer. Here, we show that the gastric tumor cell line, AGS, can respond to the PCP ligand WNT5A, however, express a very low level of the bona-fide WNT/PCP receptor, ROR2. At the same time, we find that CAF display long filopodia and had significantly higher levels of ROR2 than normal gastric fibroblasts. By high-resolution imaging, we observe a direct, cytoneme-mediated transfer of a complex containing ROR2 and WNT5A from CAF to the gastric cancer cells. The amount of ROR2 transferred correlated with JNK signaling in receiving cells, showing a direct requirement for receptor transfer. Co-culture of AGS with CAF expressing a dominant-negative form of ROR2 exhibited reduced actin polarization and migration compared to wild-type CAF. Furthermore, induction of migration via paracrine ROR2 transfer was observed in a zebrafish in vivo model. These unexpected findings demonstrate a fresh role in the direct transfer of a Wnt receptor from a signal-producing cell to a receiving cell and explain the mechanism by which gastric cancer cells expressing low levels of ROR2 can respond to a WNT5A-high tumor microenvironment.

cancer biology↗

bioRxiv2022

The production of diverse brGDGTs by an Acidobacterium allows a direct test of temperature and pH controls on their distribution

Microbial lipid biomarkers preserved in geological archives can be used to explore past climate changes. Branched glycerol dialkyl glycerol tetraethers (brGDGTs) are unique bacterial biomarkers that have been used as molecular tools for the quantitative determination of terrestrial temperatures and the pH of depositional environments over a range of geological timescales. However, the exact biological source organisms - especially of the entire suite of brGDGTs found in the environment - remains unclear; by extension, so do the mechanisms that govern these proxies. Here, we identified a brGDGT-producing strain Candidatus Solibacter usitatus Ellin6076, by identifying archaeal tetraether synthase homologs in bacterial genomes. This strain synthesizes diverse brGDGTs, including regular C5-methylated and cyclic brGDGTs, and brGDGTs comprise up to 66% of the major lipids, far exceeding the proportions found in previous studies. The degree of C5-methylation in cultured strain Ellin6076 is primarily determined by temperature, whereas cyclization appears to be influenced by multiple factors. Consequently, culture-derived paleoclimate indices are in agreement with the global soil-derived MBT5ME (methylation index of C5-methyl brGDGTs) proxy for temperature but not the CBT5ME (cyclization index of C5-methyl brGDGTs) proxy for pH. Our findings provide important insights from a physiological perspective into the underlying mechanism of brGDGT-based proxies. Significance StatementBranched glycerol dialkyl glycerol tetraethers (brGDGTs) are biomarkers widely used for the quantitative estimation of past climatic changes due to their ubiquitous occurrence in the environment and the relationships between their distributions and temperature and pH. However, the ecophysiology of brGDGT-producing bacteria and the mechanistic basis for brGDGT-based climate proxies remain unknown. Here, we identify a brGDGT-producing Acidobacterium and present a physiological study of brGDGTs in response to cultivation variables, which provides pivotal insights into how brGDGT producers modulate methylation and cyclization under different culturing conditions. Our study represents a significant advancement in understanding the physiological role of lipid structures in microbial adaptation and helps us interpret the relationships between brGDGT-based proxies and environmental conditions of the geological environment.

microbiology↗

bioRxiv2022

The catalytic domain of cellulose synthase (CESA) is involved in vesicle trafficking and protein dynamics

Cellulose, as the main component of the plant cell wall, is synthesized by a multimeric protein complex named the cellulose synthase (CESA) complex or CSC. In plant cells, CSCs are transported through the endomembrane system to the PM, but how catalytic activity or conserved motifs around the catalytic core domain influence vesicle trafficking or protein dynamics is not well understood. Here, we used a functional YFP-tagged AtCESA6 and site- directed mutagenesis to create 18 single amino acid replacement mutants in key motifs of the catalytic domain including DDG, DXD, TED and QXXRW, to comprehensively analyze how catalytic activity affects plant growth, cellulose biosynthesis, complex formation, as well as CSC dynamics and trafficking. Plant growth and cellulose content were reduced by nearly all mutations. Moreover, mutations in most conserved motifs reduced the speed of CSC movement in the PM as well as delivery of CSCs to the PM. Interestingly, the abundance of YFP-CESA6 in the Golgi apparatus was increased or reduced by mutations in DDG and QXXRW motifs, respectively. Post-Golgi trafficking of CSCs was also differentially perturbed by these mutations and, based on these phenotypes, the 18 mutations could be divided into two major groups. Group I comprises mutations causing significantly increased fluorescence intensity of YFP-CESA6 in Golgi with either an increase or no change in the abundance of cortical small CESA-containing compartments (SmaCCs). In contrast, Group II represents mutations with significantly decreased fluorescence intensity of YFP-CESA6 in Golgi and/or reduced SmaCC density. In addition, two Group II mutations in the QXXRW motif reduced CSC assembly in the Golgi. We propose that Group I mutations cause CSC trafficking defects whereas Group II mutations, especially in the QXXRW motif, affect normal CSC rosette formation in the ER or Golgi and hence interfere with subsequent CSC trafficking. Collectively, our results demonstrate that the catalytic domain of CESA6 is essential not only for cellulose biosynthesis, but also CESA complex formation, protein folding and dynamics, vesicle trafficking, or all of the above. One sentence summaryA comprehensive mutational analysis of the catalytic domain of Arabidopsis CESA6 reveals distinct roles for conserved motifs in CSC vesicle trafficking, protein complex formation, or protein dynamics

plant biology↗

bioRxiv2022

Osmotic stress via calmodulin lead to the formation of stress granule in Drosophila S2 cells.

Cellular stress of S2 cells leads to the formation of stress assemblies by phase separation of cytoplasmic components. We have shown that the cellular stresses of either high increase of the NaCl concentration in the extracellular medium, or a moderate one combined to amino acid starvation, leads to the formation of Sec bodies where components of the endoplasmic Reticulum exit sites (ERES) coalesce. These extracellular stresses lead to both the activation of salt inducible kinase (SIK), and to ER stress triggering the activation of the two downstream kinases IRE1 and PERK. Interestingly, the same stresses also result in the formation of a second stress assembly, the stress granules, which stores specific RNAs and RNA binding proteins. Here we asked whether stress granule formation is governed by the same pathways as Sec bodies. However, we found that the inhibition of SIK, IRE1 and PERK does not affect stress granule formation. Instead, we found that osmotic stress through the addition of either salts (including calcium chloride) or sucrose leads to the formation of stress granules. Interestingly, stress granule formation is partly modulated by calmodulin activation, suggesting the involvement of calcium signaling. Furthermore, as Sec body formation is driven by entirely different pathways, these results show that the same cells under the same stress, form two different stress assemblies by non-overlapping downstream pathway activation, perhaps explaining that they do not coalescence into a single structure.

cell biology↗

bioRxiv2022

Genomes of Two Flying Squid Species Provide Novel Sights into Adaptations of Cephalopods to Pelagic Life

Pelagic cephalopods have evolved a series of fascinating traits, such as excellent visual acuity, high-speed agility, and photophores for adaptation to open pelagic oceans. However, the genetic mechanisms underpinning these traits are not well understood. Thus, in this study, we obtained high-quality genomes of two purpleback flying squid species (Sthenoteuthis oualaniensis and Sthenoteuthis sp.), with sizes of 5450 and 5651 Mb. Comparative genomic analyses revealed a common expansion of the S-crystallin subfamily SL20-1 associated with visual acuity in the purpleback flying squid lineage and showed that evolution of high-speed agility for the species was accompanied by significant positive selection pressure on genes related to energy metabolism. These molecular signals might have contributed to the evolution of their adaptative predatory and anti-predatory traits. In addition, transcriptomic analysis provided clear indications of the evolution for the photophores of purpleback flying squids, inter alia that recruitment of new genes and energy metabolism genes may have played key functional roles in the process.

genomics↗

bioRxiv2022

LANTSA: Landmark-based transferable subspace analysis for single-cell and spatial transcriptomics

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) technologies provide new insights to understand tissue organization and biological function. Accurately capturing the relationships of samples (e.g., sequenced cells, spatial locations) will result in reliable and consistent outcomes in downstream analyses. However, this undertaking remains a challenge for large-volume or cross-platform datasets due to transcriptional heterogeneity and high computational demands. Here, we introduce landmark-based transferable subspace analysis (LANTSA) to solve such challenges for scRNA-seq and ST datasets. Specifically, LANTSA constructs a representation graph of samples for clustering and visualization based on a novel subspace model, which can learn a more accurate representation and is theoretically proven to be linearly proportional to data size in terms of the time consumption. Furthermore, LANTSA uses a dimensionality reduction technique as an integrative method to extract the discriminants underlying the representation structure, which enables label transfer from one (learning) dataset (i.e., scRNA-seq profiles) to the other (prediction) datasets (e.g., scRNA-seq or ST profiles), thus solving the massive-volume or cross-platform problem. We demonstrated the superiority of LANTSA to identify accurate data structures via clustering evaluation on benchmark datasets of various scRNA-seq protocols, 10x Visium, and Slide-seq ST platforms. Moreover, we confirmed the integration capability of LANTSA to transfer cell annotation on large-scale and cross-platform scRNA-seq datasets. Finally, we validated the effectiveness of LANTSA for the identification of multiple mouse brain areas as well as the spatial mapping of cell types within cortical layers by integrating scRNA-seq and ST data.

bioinformatics↗

bioRxiv2022

A chemical molecule promotes Trop2+ biliary duct organoids differentiation into insulin-secreting cells

Cell replacement therapy is a hopeful strategy for diabetes treatment, whereas lack of pancreas donors leads this strategy to a dilemma. Here, we demonstrate that Trop2 is a useful marker to enrich the progenitors with a long-term organoid formation capability from extrahepatic bile ducts in both mouse and human. Based on BMP7 initiation, the Trop2-positive mouse extrahepatic bile duct organoids (mBDOs) could be induced to produce 8.49 {+/-} 0.45% of insulin-secreting cells. We further screened out a chemical small molecule TLY142, which significantly increased the proportion of insulin-secreting cells to 19.9 {+/-} 0.62% and 25.50 {+/-} 4.82% in induced mouse and human extrahepatic bile duct organoids (hBDOs) in vitro, and transplantation of these differentiated organoids into STZ-induced diabetic nude mice remarkably improved their blood glucose and enhanced glucose sensitivity. This study provides a novel strategy that using small molecules promotes biliary duct organoids differentiation into {beta} cells to cure diabetes. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/483710v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@3c85b5org.highwire.dtl.DTLVardef@16e3874org.highwire.dtl.DTLVardef@13c509corg.highwire.dtl.DTLVardef@d0608f_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2022

Acid-Base Homeostasis and Implications to the Phenotypic Behaviors of Cancer

Acid-base homeostasis is a fundamental property of living cells and its persistent disruption in human cells can lead to a wide range of diseases. We have conducted computational modeling and analysis of transcriptomic data of 4750 human tissue samples of nine cancer types in the TCGA database. Built on our previous study, we have quantitatively estimated the (average) production rate of OH- by cytosolic Fenton reactions, which continuously disrupt the intracellular pH homeostasis. Our predictions indicate that all or a subset of 43 reprogrammed metabolisms (RMs) are induced to produce net protons (H+) at comparable rates of Fenton reactions to keep the intracellular pH stable. We have then discovered that a number of well-known phenotypes of cancers, including increased growth rate, metastasis rate and local immune cell composition, can be naturally explained in terms of the Fenton reaction level and the induced RMs. This study strongly suggests the possibility to have a unified framework for studies of cancer-inducing stressors, adaptive metabolic reprogramming, and cancerous behaviors. In addition, strong evidence is provided to demonstrate that a popular view of that Na+/H+ exchangers, along with lactic acid exporters and carbonic anhydrases are responsible for the intracellular alkalization and extracellular acidification in cancer may not be justified.

bioinformatics↗

bioRxiv2022

Alnustone inhibits Streptococcus pneumoniae virulence by targeting pneumolysin and sortase A

Streptococcus pneumoniae (S. pneumoniae) is a significant Gram-positive opportunistic pathogen responsible for a variety of lethal infections. This bacterium accounts for more deaths from diseases than any other single pathogen worldwide. Distinctively, these symptoms arise despite effective antibiotic therapy. This study unveiled a novel mechanism of resistance to S. pneumoniae infection by targeting pneumolysin (PLY) and sortase A (Srt A), the key virulence factors of S. pneumoniae. Through protein phenotype assays, we found alnustone to be a potent drug that inhibits both PLY and Srt A. Using a PLY-mediated hemolysis assay, we found that albumin can effectively reduce Srt A peptidase activity by blocking PLY oligomerization, thereby directly inhibiting PLY-expressing cytolysis. Co-incubation of S. pneumoniae D39 Srt A with small-molecule inhibitors reduces cell wall-bound Nan A (pneumococcal-anchored surface protein Srt A), inhibits biofilm formation, and significantly reduces biomass. But more interestingly, the protective effect of invasive pneumococcal disease (IPD) on murine streptococcus pneumoniae was further demonstrated. Our study proposes a detailed bacteriostatic mechanism of pneumococcal and highlights the major translational potential of targeting circulating PLY and Srt A to protect against pneumococcal infections. Our results suggest that the antiviral strategy of directly targeting PLY and Srt A with alnustone is a promising treatment option for Streptococcus pneumoniae and that alnustone can be used as an effective inhibitor of PLY and Srt A.

microbiology↗

bioRxiv2022

Gut microbiota-derived tryptamine impairs insulin sensitivity

Gut-microbiota plays a pivotal role in development of type 2 diabetes (T2D), yet the molecular mechanism remains elusive. Here, we show that tryptamine, a microbial metabolite of tryptophan, impairs glucose tolerance and insulin sensitivity. Tryptamine presents a higher level in monkeys with spontaneous diabetes and human with T2D and positively correlated with the glucose tolerance. In parallel, tryptamine level was suppressed by dietary fibers intervention in T2D subjects and negatively correlated with improvement of glucose tolerance. The inhibitory effect of tryptamine on insulin signaling as shown was dependent on a trace amine-associated receptor 1 (TAAR1)-extracellular signal-regulated kinase (ERK) signaling axis. Monoassociation of T2D-associated tryptamine-producing bacteria Ruminococcus gnavus impairs insulin sensitivity in pseudo germ-free mice. Our findings indicate gut microbiota-derived tryptamine contributes to the development of insulin resistance in T2D and may serve as a new target for intervention. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

microbiology↗

bioRxiv2022

A novel missense mutation in the proprotein convertase gene furinb causes hepatic cystogenesis during liver development in zebrafish

Hepatic cysts are fluid-filled lesions in the liver that are estimated to occur in 5% of the population. They may cause hepatomegaly and abdominal pain. Progression to secondary fibrosis, cirrhosis, or cholangiocarcinoma can lead to morbidity and mortality. Previous studies of patients and rodent models have associated hepatic cyst formation with increased proliferation and fluid secretion in cholangiocytes, which are partially due to impaired primary cilia. Congenital hepatic cysts are thought to originate from faulty bile duct development, but the underlying mechanisms are not fully understood. In a forward genetic screen, we identified a zebrafish mutant that develops hepatic cysts during larval stages. Cyst formation in these mutants is not due to changes in biliary cell proliferation, bile secretion, or impairment of primary cilia. Instead, time-lapse live imaging data showed that the mutant biliary cells failed to form interconnecting bile ducts because of defects in motility and protrusive activity. Accordingly, immunostaining revealed an excessive and disorganized actin and microtubule cytoskeleton in the mutant biliary cells. By whole-genome sequencing, we determined that the cystic phenotype in the mutant was caused by a missense mutation in the furinb gene which encodes a proprotein convertase. The mutation alters Furinb localization and causes endoplasmic reticulum (ER) stress. The cystic phenotype could be suppressed by treatment with the ER stress inhibitor 4-phenylbutyric acid and exacerbated by treatment with the ER stress inducer tunicamycin. The mutant livers also exhibited increased mTOR signaling and treatment with the mTOR inhibitor rapamycin partially blocked cyst formation by reducing ER stress. Our study has established a novel vertebrate model for studying hepatic cystogenesis and illustrated the role of ER stress in the disease pathogenesis.

developmental biology↗

bioRxiv2022

High coverage of single cell genomes by T7-assisted enzymatic methyl-sequencing

Conventional approaches to studying 5mC marks in single cells or samples with picogram input DNA amounts usually suffer from low genome coverage due to DNA degradation. Many methods have been developed to optimize the library construction efficiency for bisulfite-treated DNA. However, most of these approaches ignored the amplification bias of bisulfite-treated DNA, which leads to shallow genome coverage. In this study, we developed the T7-assisted enzymatic methyl-sequencing method (TEAM-seq), which adopts enzymatic conversion to minimize DNA degradation and T7 polymerase-assisted unbiased amplification. We demonstrate that TEAM-seq delivered, to the best of our knowledge, the highest reported coverage(70% for 100pg, 35% for 20pg) of single cell genomes in whole-genome 5mC sequencing.

genomics↗

bioRxiv2022

Fuzzy Supertertiary Interactions within PSD-95 Enable Ligand Binding

The scaffold protein PSD-95 links postsynaptic receptors to sites of presynaptic neurotransmitter release. Flexible linkers between folded domains in PSD-95 enable a dynamic supertertiary structure. Interdomain interactions within the PSG supramodule, formed by PDZ3, SH3 and GuK domains, regulate PSD-95 activity. Here we combined Discrete Molecular Dynamics and single molecule FRET to characterize the PSG supramodule, with time resolution spanning picoseconds to seconds. We used a FRET network to measure distances in full-length PSD-95 and model the conformational ensemble. We found that PDZ3 samples two conformational basins, which we confirmed with disulfide mapping. To understand effects on activity, we measured binding of the synaptic adhesion protein neuroligin. We found that PSD-95 bound neuroligin well at physiological pH while truncated PDZ3 bound poorly. Our hybrid structural models reveal how the supertertiary context of PDZ3 enables recognition of this critical synaptic ligand.

biophysics↗

bioRxiv2022

TFIIB-related factor 1 is a nucleolar protein that promotes RNA polymerase I-directed transcription and tumour cell growth

RNA polymerase I (Pol I) products play pivotal roles in ribosomal assembly, protein synthesis and cell growth. Dysregulation of Pol I product synthesis closely correlates with tumourigenesis. However, the factors and pathways governing Pol I-dependent transcription remain to be identified. Here, we report that TFIIB-related factor 1 (BRF1), a subunit of TFIIIB required for Pol III-mediated transcription, is a nucleolar protein and modulates the rRNA synthesis directed by Pol I. We show that BRF1 can be co-localized with nucleolar protein markers in several human cell types. BRF1 expression positively correlates with Pol I product levels and tumour cell growth in vitro and in vivo. Mechanistically, BRF1 binds to the Pol I transcription machinery factors and is recruited to the rDNA promoter with them. Alteration of BRF1 expression affected the recruitment of Pol I transcription machinery at the rDNA promoter, the rDNA promoter activity and expression of TBP and TAF1A, indicating that BRF1 modulates Pol I-direct transcription by controlling the expression of selective factor 1 subunits. Collectively, we demonstrate that BRF1 acts as a positive factor to regulate Pol I-directed transcription, suggesting that BRF1 can concurrently modulate Pol I and Pol III transcription and acts as a key coordinator between them.

molecular biology↗