SnF2-Catalyzed Lithiophilic-Lithiophobic Gradient Interface for High-Rate PEO-based All-Solid-State Batteries.

Polyethylene oxide (PEO)-based all solid-state lithium metal batteries (ASSLMBs) are strongly hindered by the fast dendrite growth at the Li metal/electrolyte interface, especially under large rates. The above issue stems from the suboptimal interfacial chemistry and poor Li+ transport kinetics during cycling. Herein, a SnF2-catalyzed lithiophilic-lithiophobic gradient solid electrolyte interphase (SCG-SEI) of LixSny/LiF-Li2O is in-situ formed. The superior ionic LiF-Li2O rich upper layer (17.1 nm) possesses high interfacial energy and fast Li+ diffusion channels, wherein lithiophilic LixSny alloy layer (8.4 nm) could highly reduce the nucleation overpotential with lower diffusion barrier and promote rapid electron transportation for reversible Li+ plating/stripping. Simultaneously, the insoluble SnF2-coordinated PEO promotes the rapid Li+ ion transport in the bulk phase. As a result, an over 46.7 and 3.5 times improvements for lifespan and critical current density of symmetrical cells are achieved, respectively. Furthermore, LiFePO4-based ASSLMBs deliver a recorded cycling performance at 5 C (over 1000 cycles with a capacity retention of 80.0%). More importantly, impressive electrochemical performances and safety tests with LiNi0.8Mn0.1Co0.1O2 and pouch cell with LiFePO4, even under extreme conditions (i.e., 100 ℃), are also demonstrated, reconfirmed the importance of lithiophilic-lithiophobic gradient interfacial chemistry in the design of high-rate ASSLMBs for safety applications.

Comprehensive genome-wide identification of Snf2 gene family and their expression profile under salt stress in six Brassica species of U's triangle model.

MAIN CONCLUSION: We comprehensively identified and analyzed the Snf2 gene family. Some Snf2 genes were involved in responding to salt stress based on the RNA-seq and qRT-PCR analysis. Sucrose nonfermenting 2 (Snf2) proteins are core components of chromatin remodeling complexes that not only alter DNA accessibility using the energy of ATP hydrolysis, but also play a critical regulatory role in growth, development, and stress response in eukaryotes. However, the comparative study of Snf2 gene family in the six Brassica species in U's triangle model remains unclear. Here, a total of 405 Snf2 genes were identified, comprising 53, 50, and 46 in the diploid progenitors: Brassica rapa (AA, 2n = 20), Brassica nigra (BB, 2n = 16), and Brassica oleracea (CC, 2n = 18), and 93, 91, and 72 in the allotetraploid: Brassica juncea (AABB, 2n = 36), Brassica napus (AACC, 2n = 38), and Brassica carinata (BBCC, 2n = 34), respectively. These genes were classified into six clades and further divided into 18 subfamilies based on their conserved motifs and domains. Intriguingly, these genes showed highly conserved chromosomal distributions and gene structures, indicating that few dynamic changes occurred during the polyploidization. The duplication modes of the six Brassica species were diverse, and the expansion of most Snf2 in Brassica occurred primarily through dispersed duplication (DSD) events. Additionally, the majority of Snf2 genes were under purifying selection during polyploidization, and some Snf2 genes were associated with various abiotic stresses. Both RNA-seq and qRT-PCR analysis showed that the expression of BnaSnf2 genes was significantly induced under salt stress, implying their involvement in salt tolerance response in Brassica species. The results provide a comprehensive understanding of the Snf2 genes in U's triangle model species, which will facilitate further functional analysis of the Snf2 genes in Brassica plants.

The fork remodeler helicase-like transcription factor in cancer development: all at once.

The Helicase-like Transcription Factor (HLTF) is a member of the SNF2-family of fork remodelers, primarily studied for its capacity to provide DNA Damage Tolerance (DDT) and to induce replication fork reversal (RFR). HLTF is recruited at stalled forks where both its ATPase motor and HIP116 Rad5p N-terminal (HIRAN) domains are necessary for regulating its interaction with DNA. HIRAN bestows specificity to ssDNA 3'-end and imparts branch migration as well as DNA remodeling capabilities facilitating damage repair. Both expression regulation and mutation rate affect HLTF activity. Gene hypermethylation induces loss of HLTF function, in particular in colorectal cancer (CRC), implying a tumour suppressor role. Surprisingly, a correlation between hypermethylation and HLTF mRNA upregulation has also been observed, even within the same cancer type. In many cancers, both complex mutation patterns and the presence of gene Copy Number Variations (CNVs) have been reported. These conditions affect the amount of functional HLTF and question the physiological role of this fork remodeler. This review offers a systematic collection of the presently strewed information regarding HLTF, its structural and functional characteristics, the multiple roles in DDT and the regulation in cancer progression highlighting new research perspectives.

PlantCHRs: A comprehensive database of plant chromatin remodeling factors.

The Snf2 protein family is a group of ATP-dependent chromatin remodeling factors (CHRs) that play an essential role in gene expression regulation. In plants, Snf2 is involved in growth, development, as well as stress resistance. However, only a very limited number of experimentally validated Snf2 have been identified and reported, while the majority remaining undiscovered in most species . In this study, we predicted 3135 Snf2 proteins and 8398 chromatin remodeling complex (CRC) subunits in diverse plant species, and constructed the Plant Chromatin Remodeling Factors Database (PlantCHRs, http://www.functionalgenomics.cn/PlantCHRs/), which provide a comprehensive resource for researchers to access information about plant CHRs. We also developed an online tool capable of predicting CHRs and CRC subunits. Moreover, we investigated the distribution of Snf2 proteins in different species and observed a significant increase in the number of Snf2 proteins and the diversity of the Snf2 subfamily during the evolution, highlighting their evolutionary importance. By analyzing the expression patterns of the Snf2 genes in different tissues of maize and Arabidopsis, we found that the Snf2 proteins may show some conservation across different species in regulating plant growth and development. Over the all, we established a comprehensive database for plant CHRs, which will facilitate the researches on plant chromatin remodeling.

Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking.

Single-particle cryo-EM is widely used to determine enzyme-nucleosome complex structures. However, cryo-EM sample preparation remains challenging and inconsistent due to complex denaturation at the air-water interface (AWI). To address this issue, we developed graphene-oxide-coated EM grids functionalized with either single-stranded DNA (ssDNA) or thiol-poly(acrylic acid-co-styrene) (TAASTY) co-polymer. These grids protect complexes between the chromatin remodeler SNF2h and nucleosomes from the AWI and facilitated collection of high-quality micrographs of intact SNF2h-nucleosome complexes in the absence of crosslinking. The data yields maps ranging from 2.3 to 3 Å in resolution. 3D variability analysis reveals nucleotide-state linked conformational changes in SNF2h bound to a nucleosome. In addition, the analysis provides structural evidence for asymmetric coordination between two SNF2h protomers acting on the same nucleosome. We envision these grids will enable similar detailed structural analyses for other enzyme-nucleosome complexes and possibly other protein-nucleic acid complexes in general.

A dual-function SNF2 protein drives chromatid resolution and nascent transcripts removal in mitosis.

Mitotic chromatin is largely assumed incompatible with transcription due to changes in the transcription machinery and chromosome architecture. However, the mechanisms of mitotic transcriptional inactivation and their interplay with chromosome assembly remain largely unknown. By monitoring ongoing transcription in Drosophila early embryos, we reveal that eviction of nascent mRNAs from mitotic chromatin occurs after substantial chromosome compaction and is not promoted by condensin I. Instead, we show that the timely removal of transcripts from mitotic chromatin is driven by the SNF2 helicase-like protein Lodestar (Lds), identified here as a modulator of sister chromatid cohesion defects. In addition to the eviction of nascent transcripts, we uncover that Lds cooperates with Topoisomerase 2 to ensure efficient sister chromatid resolution and mitotic fidelity. We conclude that the removal of nascent transcripts upon mitotic entry is not a passive consequence of cell cycle progression and/or chromosome compaction but occurs via dedicated mechanisms with functional parallelisms to sister chromatid resolution.

Missense variant in SRCAP with distinct DNA methylation signature associated with non-FLHS SRCAP-related neurodevelopmental disorder.

Floating-Harbor syndrome (FLHS) is a neurodevelopmental disorder (NDD) caused by truncating variants in exons 33 and 34 of the SNF2-related CREBBP activator protein gene (SRCAP). Truncating variants proximal to this location in SRCAP result in a non-FLHS SRCAP-associated NDD; an overlapping but distinct NDD characterized by developmental delay with or without intellectual disability (ID), hypotonia, normal stature, and behavioral and psychiatric issues. Here, we report a young woman who initially presented in childhood with significant delays in speech and mild ID. In young adulthood, she developed schizophrenia. On physical examination, she had facial features suggestive of 22q11 deletion syndrome. After non-diagnostic chromosomal microarray and trio exome sequencing (ES), a re-analysis of trio ES data identified a de novo missense variant in SRCAP that was proximal to the FLHS critical region. Subsequent DNA methylation studies showed the unique methylation signature associated with pathogenic sequence variants in non-FLHS SRCAP-related NDD. This clinical report describes an individual with non-FLHS SRCAP-related NDD caused by an SRCAP missense variant, and it also demonstrates the clinical utility of ES re-analysis and DNA methylation analysis for undiagnosed patients, in particular, those with variants of uncertain significance.

Synthesis and Improved Photoluminescence of SnF2-Derived CsSnCl3-SnF2:Mn2+ Perovskites via Rapid Thermal Treatment.

We report a rapid synthesis method for producing CsSnCl3:Mn2+ perovskites, derived from SnF2, and investigate the effects of rapid thermal treatment on their photoluminescence properties. Our study shows that the initial CsSnCl3:Mn2+ samples exhibit a double luminescence peak structure with PL peaks at approximately 450 nm and 640 nm, respectively. These peaks originate from defect-related luminescent centers and the 4T1→6A1 transition of Mn2+. However, as a result of rapid thermal treatment, the blue emission is significantly reduced and the red emission intensity is increased nearly twofold compared to the pristine sample. Furthermore, the Mn2+-doped samples demonstrate excellent thermal stability after the rapid thermal treatment. We suggest that this improvement in photoluminescence results from enhanced excited-state density, energy transfer between defects and the Mn2+ state, as well as the reduction of nonradiative recombination centers. Our findings provide valuable insights into the luminescence dynamics of Mn2+-doped CsSnCl3 and open up new possibilities for controlling and optimizing the emission of rare-earth-doped CsSnCl3.

Differentiation of Plasmodium male gametocytes is initiated by the recruitment of a chromatin remodeler to a male-specific cis-element.

Plasmodium parasites, the causative agents of malaria, possess a complex lifecycle; however, the mechanisms of gene regulation involved in the cell-type changes remain unknown. Here, we report that gametocyte sucrose nonfermentable 2 (gSNF2), an SNF2-like chromatin remodeling ATPase, plays an essential role in the differentiation of male gametocytes. Upon disruption of gSNF2, male gametocytes lost the capacity to develop into gametes. ChIP-seq analyses revealed that gSNF2 is widely recruited upstream of male-specific genes through a five-base, male-specific cis-acting element. In gSNF2-disrupted parasites, expression of over a hundred target genes was significantly decreased. ATAC-seq analysis demonstrated that decreased expression of these genes correlated with a decrease of the nucleosome-free region upstream of these genes. These results suggest that global changes induced in the chromatin landscape by gSNF2 are the initial step in male differentiation from early gametocytes. This study provides the possibility that chromatin remodeling is responsible for cell-type changes in the Plasmodium lifecycle.

Genome-Wide Identification and Characterization of the Soybean Snf2 Gene Family and Expression Response to Rhizobia.

Sucrose nonfermenting 2 (Snf2) family proteins are the core component of chromatin remodeling complexes that can alter chromatin structure and nucleosome position by utilizing the energy of ATP, playing a vital role in transcription regulation, DNA replication, and DNA damage repair. Snf2 family proteins have been characterized in various species including plants, and they have been found to regulate development and stress responses in Arabidopsis. Soybean (Glycine max) is an important food and economic crop worldwide, unlike other non-leguminous crops, soybeans can form a symbiotic relationship with rhizobia for biological nitrogen fixation. However, little is known about Snf2 family proteins in soybean. In this study, we identified 66 Snf2 family genes in soybean that could be classified into six groups like Arabidopsis, unevenly distributed on 20 soybean chromosomes. Phylogenetic analysis with Arabidopsis revealed that these 66 Snf2 family genes could be divided into 18 subfamilies. Collinear analysis showed that segmental duplication was the main mechanism for expansion of Snf2 genes rather than tandem repeats. Further evolutionary analysis indicated that the duplicated gene pairs had undergone purifying selection. All Snf2 proteins contained seven domains, and each Snf2 protein had at least one SNF2_N domain and one Helicase_C domain. Promoter analysis revealed that most Snf2 genes had cis-elements associated with jasmonic acid, abscisic acid, and nodule specificity in their promoter regions. Microarray data and real-time quantitative PCR (qPCR) analysis revealed that the expression profiles of most Snf2 family genes were detected in both root and nodule tissues, and some of them were found to be significantly downregulated after rhizobial infection. In this study, we conducted a comprehensive analysis of the soybean Snf2 family genes and demonstrated their responsiveness to Rhizobia infection. This provides insight into the potential roles of Snf2 family genes in soybean symbiotic nodulation.

Chromatin Remodeling Enzyme Snf2h Is Essential for Retinal Cell Proliferation and Photoreceptor Maintenance.

Chromatin remodeling complexes are required for many distinct nuclear processes such as transcription, DNA replication, and DNA repair. However, the contribution of these complexes to the development of complex tissues within an organism is poorly characterized. Imitation switch (ISWI) proteins are among the most evolutionarily conserved ATP-dependent chromatin remodeling factors and are represented by yeast Isw1/Isw2, and their vertebrate counterparts Snf2h (Smarca5) and Snf2l (Smarca1). In this study, we focused on the role of the Snf2h gene during the development of the mammalian retina. We show that Snf2h is expressed in both retinal progenitors and post-mitotic retinal cells. Using Snf2h conditional knockout mice (Snf2h cKO), we found that when Snf2h is deleted, the laminar structure of the adult retina is not retained, the overall thickness of the retina is significantly reduced compared with controls, and the outer nuclear layer (ONL) is completely missing. The depletion of Snf2h did not influence the ability of retinal progenitors to generate all the differentiated retinal cell types. Instead, the Snf2h function is critical for the proliferation of retinal progenitor cells. Cells lacking Snf2h have a defective S-phase, leading to the entire cell division process impairments. Although all retinal cell types appear to be specified in the absence of the Snf2h function, cell-cycle defects and concomitantly increased apoptosis in Snf2h cKO result in abnormal retina lamination, complete destruction of the photoreceptor layer, and consequently, a physiologically non-functional retina.

ERCC6L2 mitigates replication stress and promotes centromere stability.

Structurally complex genomic regions, such as centromeres, are inherently difficult to duplicate. The mechanism behind centromere inheritance is not well understood, and one of the key questions relates to the reassembly of centromeric chromatin following DNA replication. Here, we define ERCC6L2 as a key regulator of this process. ERCC6L2 accumulates at centromeres and promotes deposition of core centromeric factors. Interestingly, ERCC6L2-/- cells show unrestrained replication of centromeric DNA, likely caused by the erosion of centromeric chromatin. Beyond centromeres, ERCC6L2 facilitates replication at genomic repeats and non-canonical DNA structures. Notably, ERCC6L2 interacts with the DNA-clamp PCNA through an atypical peptide, presented here in a co-crystal structure. Finally, ERCC6L2 also restricts DNA end resection, acting independently of the 53BP1-REV7-Shieldin complex. We propose a mechanistic model, which reconciles seemingly distinct functions of ERCC6L2 in DNA repair and DNA replication. These findings provide a molecular context for studies linking ERCC6L2 to human disease.

Snf2 Proteins Are Required to Generate Gamete Pronuclei in Tetrahymena thermophila.

During sexual reproduction/conjugation of the ciliate Tetrahymena thermophila, the germinal micronucleus undergoes meiosis resulting in four haploid micronuclei (hMICs). All hMICs undergo post-meiotic DNA double-strand break (PM-DSB) formation, cleaving their genome. DNA lesions are subsequently repaired in only one 'selected' hMIC, which eventually produces gametic pronuclei. DNA repair in the selected hMIC involves chromatin remodeling by switching from the heterochromatic to the euchromatic state of its genome. Here, we demonstrate that, among the 15 Tetrahymena Snf2 family proteins, a core of the ATP-dependent chromatin remodeling complex in Tetrahymena, the germline nucleus specific Iswi in Tetrahymena IswiGTt and Rad5Tt is crucial for the generation of gametic pronuclei. In either gene knockout, the selected hMIC which shows euchromatin markers such as lysine-acetylated histone H3 does not appear, but all hMICs in which markers for DNA lesions persist are degraded, indicating that both IswiGTt and Rad5Tt have important roles in repairing PM-DSB DNA lesions and remodeling chromatin for the euchromatic state in the selected hMIC.

Cockayne syndrome group B protein uses its DNA translocase activity to promote mitotic DNA synthesis.

Mitotic DNA synthesis, also known as MiDAS, has been suggested to be a form of RAD52-dependent break-induced replication (BIR) that repairs under-replicated DNA regions of the genome in mitosis prior to chromosome segregation. Cockayne syndrome group B (CSB) protein, a chromatin remodeler of the SNF2 family, has been implicated in RAD52-dependent BIR repair of stalled replication forks. However, whether CSB plays a role in MiDAS has not been characterized. Here, we report that CSB functions epistatically with RAD52 to promote MiDAS at common fragile sites in response to replication stress, and prevents genomic instability associated with defects in MiDAS. We show that CSB is dependent upon the conserved phenylalanine at position 796 (F796), which lies in the recently-reported pulling pin that is required for CSB's translocase activity, to mediate MiDAS, suggesting that CSB uses its DNA translocase activity to promote MiDAS. Structural analysis reveals that CSB shares with a subset of SNF2 family proteins a translocase regulatory region (TRR), which is important for CSB's function in MiDAS. We further demonstrate that phosphorylation of S1013 in the TRR regulates the function of CSB in MiDAS and restart of stalled forks but not in fork degradation in BRCA2-deficient cells and UV repair. Taken together, these results suggest that the DNA translocase activity of CSB in vivo is likely to be highly regulated by post-translational modification in a context-specific manner.

Comparative Expression Profiling of Snf2 Family Genes During Reproductive Development and Stress Responses in Rice.

Sucrose non-fermenting 2 (Snf2) protein family, as chromatin remodeling factors, is an enormous and the most diverse protein family, which contributes to biological processes of replication, transcription, and DNA repair using the energy of adenosine triphosphate (ATP) hydrolysis. The members of Snf2 family proteins have been well characterized in Arabidopsis, rice, and tomato. Although this family received significant attention, few genes were identified uniquely for their roles in mediating reproductive development and stress tolerance in rice. In the present study, we comprehensively analyzed the expression profiling of Snf2 genes during reproductive development and biotic/abiotic stresses. Our results showed that five proteins (OsCHR712/715/720/726/739) were mainly localized in the nucleus, while OsCHR715/739 were also slightly expressed in the cell membrane. There were abundant cis-acting elements in the putative promoter of Snf2 genes, including dehydration, MeJA, MYB binding site for drought, ABA-responsive, and stress-responsive element. Most of the genes were induced immediately after Magnaporthe oryzae infection at 12 h post-infection (hpi). About 55% of the total genes were upregulated under salt and drought stresses during the entire time, and 22-35% of the total genes were upregulated at 3 h. It was noteworthy that the seven genes (OsCHR705, OsCHR706, OsCHR710, OsCHR714, OsCHR721, OsCHR726, and OsCHR737) were upregulated, and one gene (OsCHR712) was downregulated under salt and drought stresses, respectively. The deficiency of OsCHR726 mutations displayed a hypersensitive phenotype under salt stress. These results will be significantly useful features for the validation of the rice Snf2 genes and facilitate understanding of the genetic engineering of crops with improved biotic and abiotic stresses.

OsDDM1b Controls Grain Size by Influencing Cell Cycling and Regulating Homeostasis and Signaling of Brassinosteroid in Rice.

Snf2 family proteins are the crucial subunits of chromatin-remodeling complexes (CRCs), which contributes to the biological processes of transcription, replication, and DNA repair using ATP as energy. Some CRC subunits have been confirmed to be the critical regulators in various aspects of plant growth and development and in epigenetic mechanisms such as histone modification, DNA methylation, and histone variants. However, the functions of Snf2 family genes in rice were poorly investigated. In this study, the relative expression profile of 40 members of Snf2 family in rice was studied at certain developmental stages of seed. Our results revealed that OsCHR741/OsDDM1b (Decrease in DNA methylation 1) was accumulated highly in the early developmental stage of seeds. We further analyzed the OsDDM1b T-DNA insertion loss-of-function of mutant, which exhibited dwarfism, smaller organ size, and shorter and wider grain size than the wild type (Hwayoung, HY), yet no difference in 1,000-grain weight. Consistent with the grain size, the outer parenchyma cell layers of lemma in osddm1b developed more cells with decreased size. OsDDM1b encoded a nucleus, membrane-localized protein and was distributed predominately in young spikelets and seeds, asserting its role in grain size. Meanwhile, the osddm1b was less sensitive to brassinosteroids (BRs) while the endogenous BR levels increased. We detected changes in the expression levels of the BR signaling pathway and feedback-inhibited genes with and without exogenous BR application, and the alterations of expression were also observed in grain size-related genes in the osddm1b. Altogether, our results suggest that OsDDM1b plays a crucial role in grain size via influencing cell proliferation and regulating BR signaling and homeostasis.

Chromatin Remodeler Smarca5 Is Required for Cancer-Related Processes of Primary Cell Fitness and Immortalization.

Smarca5, an ATPase of the ISWI class of chromatin remodelers, is a key regulator of chromatin structure, cell cycle and DNA repair. Smarca5 is deregulated in leukemia and breast, lung and gastric cancers. However, its role in oncogenesis is not well understood. Chromatin remodelers often play dosage-dependent roles in cancer. We therefore investigated the epigenomic and phenotypic impact of controlled stepwise attenuation of Smarca5 function in the context of primary cell transformation, a process relevant to tumor formation. Upon conditional single- or double-allele Smarca5 deletion, the cells underwent both accelerated growth arrest and senescence entry and displayed gradually increased sensitivity to genotoxic insults. These phenotypic characteristics were explained by specific remodeling of the chromatin structure and the transcriptome in primary cells prior to the immortalization onset. These molecular programs implicated Smarca5 requirement in DNA damage repair, telomere maintenance, cell cycle progression and in restricting apoptosis and cellular senescence. Consistent with the molecular programs, we demonstrate for the first time that Smarca5-deficient primary cells exhibit dramatically decreased capacity to bypass senescence and immortalize, an indispensable step during cell transformation and cancer development. Thus, Smarca5 plays a crucial role in key homeostatic processes and sustains cancer-promoting molecular programs and cellular phenotypes.

Structural insights into DNMT5-mediated ATP-dependent high-fidelity epigenome maintenance.

Epigenetic evolution occurs over million-year timescales in Cryptococcus neoformans and is mediated by DNMT5, the first maintenance type cytosine methyltransferase identified in the fungal or protist kingdoms, the first dependent on adenosine triphosphate (ATP), and the most hemimethyl-DNA-specific enzyme known. To understand these novel properties, we solved cryo-EM structures of CnDNMT5 in three states. These studies reveal an elaborate allosteric cascade in which hemimethylated DNA binding first activates the SNF2 ATPase domain by a large rigid body rotation while the target cytosine partially flips out of the DNA duplex. ATP binding then triggers striking structural reconfigurations of the methyltransferase catalytic pocket to enable cofactor binding, completion of base flipping, and catalysis. Bound unmethylated DNA does not open the catalytic pocket and is instead ejected upon ATP binding, driving high fidelity. This unprecedented chaperone-like, enzyme-remodeling role of the SNF2 ATPase domain illuminates how energy is used to enable faithful epigenetic memory.

Characterization of integrative and conjugative elements carrying antibiotic resistance genes of Streptococcus suis isolated in China.

Streptococcus suis, an emerging zoonotic pathogen, is important reservoirs of antibiotic resistance genes that play critical roles in the horizontal transfer of corresponding resistances. In the present study, 656 antibiotic resistance (AR) genes were detected in 154 of 155 genomes of S. suis strains isolated from the nasopharynx of slaughtered pigs and the lungs of diseased pigs in China. The AR genes were clustered into 11 categories, consisting of tetracycline, macrolides, lincosamide, streptogramin, aminoglycoside, trimethoprim, amphenicols, nucleoside, quinupristin/dalfopristin, glycopeptide, and oxazolidinones resistance genes. In order to investigate the transmission patterns of the AR genes, AR genes-associated the mobile genetic elements (MGEs) were extracted and investigated. Twenty ICEs, one defective ICE, one tandem ICE, and ten prophages were found, which mainly carried tetracycline, macrolides/lincosamides/streptogramin (MLS), and aminoglycosides resistance genes. Three types of DNA cargo with AR genes were integrated into specific sites of ICEs: integrative mobilizable elements (IMEs), cis-IMEs (CIMEs), and transposon Tn916. Obvious differences in AR gene categories were found among the three cargo types. IMEs mainly harbored tetracycline and MLS resistance genes. CIMEs mainly carried aminoglycoside resistance genes, while transposon Tn916 carried only the tet (M) gene. Nearly all AR genes in ICEs were carried by IMEs and CIMEs. IMEs were prevalent and were also detected in additional 29 S. suis genomes. The horizontal transfer of IMEs and CIMEs may play critical role in ICE evolution and AR gene transmission in the S. suis population. Our findings provide novel insights into the transmission patterns of AR genes and the evolutionary mechanisms of ICEs in S. suis.

Multiple roles for PARP1 in ALC1-dependent nucleosome remodeling.

The SNF2 family ATPase Amplified in Liver Cancer 1 (ALC1) is the only chromatin remodeling enzyme with a poly(ADP-ribose) (PAR) binding macrodomain. ALC1 functions together with poly(ADP-ribose) polymerase PARP1 to remodel nucleosomes. Activation of ALC1 cryptic ATPase activity and the subsequent nucleosome remodeling requires binding of its macrodomain to PAR chains synthesized by PARP1 and NAD+ A key question is whether PARP1 has a role(s) in ALC1-dependent nucleosome remodeling beyond simply synthesizing the PAR chains needed to activate the ALC1 ATPase. Here, we identify PARP1 separation-of-function mutants that activate ALC1 ATPase but do not support nucleosome remodeling by ALC1. Investigation of these mutants has revealed multiple functions for PARP1 in ALC1-dependent nucleosome remodeling and provides insights into its multifaceted role in chromatin remodeling.