Search Results (21)

ATP-dependent chromatin remodeling complexes regulate gene expression by altering chromatin structure through ATP hydrolysis. They are classified into four families—SWI/SNF, ISWI, CHD, and INO80—which remodel chromatin via nucleosome sliding, eviction, assembly, and editing to control transcription. These complexes play critical roles in DNA repair, tumorigenesis, and organogenesis. Recent advances in low-input proteomics have highlighted their importance in vertebrate embryonic development. In mammals, they regulate embryonic genome activation, lineage specification, and stem cell fate determination. In non-mammalian models (e.g., Xenopus laevis), they function from blastocyst formation to pre-organogenesis stages (gastrulation and neurulation)—key windows for chromatin reprogramming and cell fate decisions. This review provides a systematic overview of chromatin remodeling complexes, detailing their classification and conserved mechanisms, and discusses their functions in early embryogenesis and embryonic stem cell maintenance. The collective evidence underscores the implications of these chromatin remodelers for understanding developmental defects and advancing regenerative medicine. Full article

Cell cycle progression of the yeast Saccharomyces cerevisiae is largely driven by the expression of cyclins, which in turn bind the cyclin-dependent kinase CDK1 providing specificity. Due to the duplication of the yeast genome during evolution, most of the cyclins are present as a pair of paralogues, which are considered to have similar functions and periods of expression. Here, we use single molecule inexpensive fluorescence in situ hybridization (smiFISH) to measure the expression of five pairs of paralogous genes relevant for cell cycle progression (CLN1/CLN2, CLB5/CLB6, CLB3/CLB4, CLB1/CLB2 and ACE2/SWI5) in a large number of unsynchronized single cells representing all cell cycle phases. We systematically compare their expression patterns and strengths. In addition, we also analyze the effect of the knockout of one part of each pair on the expression of the other gene. In order to classify cells into specific cell cycle phases, we developed a convolutional neural network (CNN). We find that the expression levels of some cell-cycle related paralogues differ in their correlation, with CLN1 and CLN2 showing strong correlation and CLB3 and CLB4 showing weakest correlation. The temporal profiles of some pairs also differ. Upon deletion of their paralogue, CLB1 and CLB2 seem to compensate for the expression of the other gene, while this was not observed for ACE2/SWI5. Interestingly, CLB1 and CLB2 also seem to share work between mother and bud in the G2 phase, where CLB2 is primarily expressed in the bud and CLB1 in the mother. Taken together, our results suggest that paralogues related to yeast cell cycle progression should not be considered as the same but differ both in their expression strength and timing as well in their precise role in cell cycle regulation. Full article

Kluyveromyces marxianus is an attractive thermotolerant yeast species for ethanol production because of its ability to utilize various carbon sources as a fermentation substrate. The use of thermotolerant microorganisms enables the performance of high-temperature ethanol fermentation, which has several advantages, including the reduction of cooling costs and minimization of contamination risks. To improve K. marxianus for ethanol fermentation under stress conditions, two strains, DMKU 3-1042 and DMKU 3-118, were adapted for heat resistance and resistance to toxic substances in pulp wastewater from a paper mill, respectively, resulting in the generation of KMR1042 and KMR118, respectively. Both adapted mutants exhibited clumpy clusters of cells as pseudo-hyphae and altered colony morphology, and their sedimentation speeds were much faster than those of the corresponding parent strains. The two mutants showed stronger tolerance to various stresses and higher performance for ethanol production than those of the corresponding parent strains at high temperatures or in the presence of toxic substances. Genome sequencing analysis revealed that both mutants had disruption of the same gene, SWI5, despite adaptation under different stress conditions, suggesting that the formation of pseudo-hyphae is a common strategy of K. marxianus for coping with stresses. Full article

Intact stability represents one of the most important topics when addressing ship safety, and it is ruled by the IMO Intact Stability code, evaluating ship stability in a calm water scenario. However, the interest in ship stability in waves has increased in recent years and this has led to the formulation of the second generation intact stability criteria (SGISc), finalized at IMO in 2020. In this research, an approach to quantitatively and comprehensively evaluate the ship stability performance in waves has been pursued. A methodology is developed with reference to the SGISc. The intact stability in waves index (ISWI) has been proposed, with the aim to become a complementary tool for designers and shipbuilders in the assessment of stability performance in waves. The ISWI represents a comprehensive stability index, able to capture the stability in waves performance of a vessel. The stability index has been verified on a set of megayacht units and its sensitivity to the wave characteristics has been tested, changing the environmental conditions. The outcomes point to a good agreement between the ISWI and the influence of environmental condition changes on the stability performance. Full article

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. Full article

During transcription, DNA replication and repair, chromatin structure is constantly modified to reveal specific genetic regions and allow access to DNA-interacting enzymes. ATP-dependent chromatin remodelling complexes use the energy of ATP hydrolysis to modify chromatin architecture by repositioning and rearranging nucleosomes. These complexes are defined by a conserved SNF2-like, catalytic ATPase subunit and are divided into four families: CHD, SWI/SNF, ISWI and INO80. ATP-dependent chromatin remodellers are crucial in regulating development and stem cell biology in numerous organs, including the inner ear. In addition, mutations in genes coding for proteins that are part of chromatin remodellers have been implicated in numerous cases of neurosensory deafness. In this review, we describe the composition, structure and functional activity of these complexes and discuss how they contribute to hearing and neurosensory deafness. Full article

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 IswiG^Tt and Rad5^Tt 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 IswiG^Tt and Rad5^Tt have important roles in repairing PM-DSB DNA lesions and remodeling chromatin for the euchromatic state in the selected hMIC. Full article

Ovarian cancer (OC) is the fifth leading cause of women’s death from cancers. The high mortality rate is attributed to the late presence of the disease and the lack of modern diagnostic tools, including molecular biomarkers. Moreover, OC is a highly heterogeneous disease, which contributes to early treatment failure. Thus, exploring OC molecular mechanisms could significantly enhance our understanding of the disease and provide new treatment options. Chromatin remodeling complexes (CRCs) are ATP-dependent molecular machines responsible for chromatin reorganization and involved in many DNA-related processes, including transcriptional regulation, replication, and reparation. Dysregulation of chromatin remodeling machinery may be related to cancer development and chemoresistance in OC. Some forms of OC and other gynecologic diseases have been associated with mutations in specific CRC genes. Most notably, ARID1A in endometriosis-related OC, SMARCA4, and SMARCB1 in hypercalcemic type small cell ovarian carcinoma (SCCOHT), ACTL6A, CHRAC1, RSF1 amplification in high-grade serous OC. Here we review the available literature on CRCs’ involvement in OC to improve our understanding of its development and investigate CRCs as possible biomarkers and treatment targets for OC. Full article

Long non-coding RNAs (lncRNAs) have been identified as key regulators of gene expression and participate in many vital physiological processes. Chromatin remodeling, being an important epigenetic modification, has been identified in many biological activities as well. However, the regulatory mechanism of lncRNA in chromatin remodeling remains unclear. In order to characterize the genome-wide lncRNA expression and their potential interacting factors during this process in Drosophila, we investigated the expression pattern of lncRNAs and mRNAs based on the transcriptome analyses and found significant differences between lncRNAs and mRNAs. Then, we performed TSA-FISH experiments of candidate lncRNAs and their potential interactors that have different functions in Drosophila embryos to determine their expression pattern. In addition, we also analyzed the expression of transposable elements (TEs) and their interactors to explore their expression in ISWI mutants. Our results provide a new perspective for understanding the possible regulatory mechanism of lncRNAs and TEs as well as their targets in chromatin remodeling. Full article

The tomato leaf miner (Tuta absoluta) is one of the top 20 plant pests worldwide. We cloned and identified the chromatin-remodelling ATPase genes ISWI and BRM by RACE and bioinformatic analysis, respectively; used RT-qPCR to examine their expression patterns during different life cycle stages; and elucidated their roles in insect reproduction using double-stranded RNA injections. The full-length cDNA of TaISWI was 3428 bp and it encoded a 1025-aa polypeptide. The partial-length cDNA of TaBRM was 3457 bp and it encoded a 1030-aa polypeptide. TaISWI and TaBRM were upregulated at the egg stage. Injection of TaISWI or TaBRM dsRNA at the late pupa stage significantly inhibited adult ovary development and reduced fecundity, hatchability, and longevity in the adult females. To the best of our knowledge, the present study was the first to perform molecular characterisations of two chromatin-remodelling ATPase genes and clarify their roles in T. absoluta fecundity. Chromatin-remodelling ATPases are potential RNAi targets for the control of T. absoluta and other insect pests. The present study was also the first to demonstrate the feasibility of reproductive inhibitory RNAi as a putative approach for the suppression of T. absoluta and other Lepidopteran insect populations. Full article

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. Full article

The bromodomain adjacent to the zinc finger domain 1B (BAZ1B) or Williams syndrome transcription factor (WSTF) are just two of the names referring the same protein that is encoded by the WBSCR9 gene and is among the 26–28 genes that are lost from one copy of 7q11.23 in Williams syndrome (WS: OMIM 194050). Patients afflicted by this contiguous gene deletion disorder present with a range of symptoms including cardiovascular complications, developmental defects as well as a characteristic cognitive and behavioral profile. Studies in patients with atypical deletions and mouse models support BAZ1B hemizygosity as a contributing factor to some of the phenotypes. Focused analysis on BAZ1B has revealed this to be a versatile nuclear protein with a central role in chromatin remodeling through two distinct complexes as well as being involved in the replication and repair of DNA, transcriptional processes involving RNA Polymerases I, II, and III as well as possessing kinase activity. Here, we provide a comprehensive review to summarize the many aspects of BAZ1B function including its recent link to cancer. Full article

The establishment and maintenance of genome packaging into chromatin contribute to define specific cellular identity and function. Dynamic regulation of chromatin organization and nucleosome positioning are critical to all DNA transactions—in particular, the regulation of gene expression—and involve the cooperative action of sequence-specific DNA-binding factors, histone modifying enzymes, and remodelers. Remodelers are molecular machines that generate various chromatin landscapes, adjust nucleosome positioning, and alter DNA accessibility by using ATP binding and hydrolysis to perform DNA translocation, which is highly regulated through sophisticated structural and functional conversations with nucleosomes. In this review, I first present the functional and structural diversity of remodelers, while emphasizing the basic mechanism of DNA translocation, the common regulatory aspects, and the hand-in-hand progressive increase in complexity of the regulatory conversations between remodelers and nucleosomes that accompanies the increase in challenges of remodeling processes. Next, I examine how, through nucleosome positioning, remodelers guide the regulation of gene expression. Finally, I explore various aspects of how alterations/mutations in remodelers introduce dissonance into the conversations between remodelers and nucleosomes, modify chromatin organization, and contribute to oncogenesis. Full article

In higher order organisms, the genome is assembled into a protein-dense structure called chromatin. Chromatin is spatially organized in the nucleus through hierarchical folding, which is tightly regulated both in cycling cells and quiescent cells. Assembly and folding are not one-time events in a cell’s lifetime; rather, they are subject to dynamic shifts to allow changes in transcription, DNA replication, or DNA damage repair. Chromatin is regulated at many levels, and recent tools have permitted the elucidation of specific factors involved in the maintenance and regulation of the three-dimensional (3D) genome organization. In this review/perspective, we aim to cover the potential, but relatively unelucidated, crosstalk between 3D genome architecture and the ATP-dependent chromatin remodelers with a specific focus on how the architectural proteins CTCF and cohesin are regulated by chromatin remodeling. Full article

Eukaryotic genomes are pervasively transcribed, producing both coding and non-coding RNAs (ncRNAs). ncRNAs are diverse and a critical family of biological molecules, yet much remains unknown regarding their functions and mechanisms of regulation. ATP-dependent nucleosome remodeling complexes, in modifying chromatin structure, play an important role in transcriptional regulation. Recent findings show that ncRNAs regulate nucleosome remodeler activities at many levels and that ncRNAs are regulatory targets of nucleosome remodelers. Further, a series of recent screens indicate this network of regulatory interactions is more expansive than previously appreciated. Here, we discuss currently described regulatory interactions between ncRNAs and nucleosome remodelers and contextualize their biological functions. Full article