Genes to Cells

Nucleoli and centromeres play essential roles in cellular proliferation and homeostasis, and are structurally and functionally interconnected. Centromeres frequently cluster around nucleoli, and some centromere assembly factors are known to reside in the nucleoli. To investigate the spatial and temporal relationships between these nuclear domains, we examined their dynamics in living cells. We imaged HeLa cells stably expressing mCherry-NPM1 and GFP-CENP-A using time-lapse microscopy. The results show that a subset of centromeres exhibits dynamic behavior during interphase, migrating over micrometer-scale distances within two hours. On average, 40-50% of centromeres maintain an association with nucleoli throughout interphase, with some cells displaying nucleolar-centromere association and dissociation within hours. Upon entry into mitosis, nucleoli are disassembled, and NPM1 localizes to the periphery of mitotic chromosomes. Nucleolar-centromere interactions are re-established in early G1, coinciding with the assembly of new centromeres. Treatment with actinomycin D, an inhibitor of RNA polymerase I, significantly reduces nucleolar size, nucleolar-centromere interactions, and centromere dynamics. Furthermore, post-mitotic nucleolar reformation is impaired. These findings highlight the dynamic nature of centromeres in interphase nuclei and their interactions with nucleoli. This behavior is partially dependent on rDNA transcription and nucleolar integrity, underscoring the critical roles of nucleoli, centromeres, and their interaction in 4D genome organization.

The actin polymerization machinery, comprising the ARP2/3 complex and its activators, the WASP family proteins, has been implicated in regulating a broad spectrum of nuclear processes, such as transcriptional regulation and nuclear organization. Here, using clustered protocadherin (cPcdh) and {beta}-globin genes as model systems, we showed that WAVE2, a member of the WASP family, regulates chromatin organization by maintaining heterochromatin dynamics. Specifically, by CRISPR DNA-fragment editing, in conjunction with integrated analyses of ChIP-seq, MeDIP-seq, ATAC-seq, 4C-seq, and RNA-seq, we showed that deposition of H3K9me3, a key heterochromatin mark, is significantly decreased at the cPcdh locus upon WAVE2 deletion, concurrent with aberrant accumulation of CTCF/cohesin complex at promoter regions and spatial reorganization of chromatin architecture around nucleolus. In addition, REST/NRSF exerts a similar heterochromatindependent effect on the cPcdh locus. Finally, genetic and genomic data showed that WAVE2 regulates {beta}-globin gene expression by maintaining heterochromatin status. Together our data suggested that WAVE2 and REST/NRSF regulate clustered gene expression in a heterochromatin-dependent manner.

The cell cycle comprises different phases and is a tightly regulated process at the molecular level. During the cell cycle, two key events occurred: DNA duplication during the S phase and chromosome segregation during mitosis. Accurate cell cycle progression, achieved through faithful chromosome segregation, is essential for maintaining cell fidelity. Long noncoding RNAs are a subclass of noncoding RNA that are longer than 200 bp and form RNA protein complexes (RNPs) to regulate various biological processes. Herein, we demonstrate that lncRNA NORM is involved in regulating the cell cycle by maintaining proper chromosome segregation. NORM exhibited G2 phase-specific expression, and the depletion of NORM resulted in a significant G2/M arrest. NORM-depleted cells failed to progress in mitosis and showed defects in chromosome segregation. We further demonstrated that NORM binds to proteins such as Plk1 and Nsun2. Depletion of NORM hindered the interaction between Plk1 and Bub1, resulting in reduced kinetochore localization of Plk1 during prometaphase. Our results also show that the depletion of NORM affects the binding of Nsun2 protein to CDK1 mRNA and, consequently, the stabilization of CDK1 at the protein level. Altogether, our results demonstrate that NORM regulates chromosome segregation by mediating the interaction between Plk1 and Bub1.

Copines are a family of calcium-dependent phospholipid-binding proteins found in most eukaryotes. The expression of multiple copine genes is dysregulated in various types of human cancers. Despite this, a common mechanistic function for copines remains unknown. We are studying copines in Dictyostelium discoideum, which has six copine genes (cpnA-cpnF). Cells lacking cpnA or cpnC (cpnA- and cpnC-, respectively) exhibit many phenotypes, including defects in development, chemotaxis, adhesion, and contractile vacuole (CV) function. To further characterize the function of copines, this study tested the hypothesis that CpnD is responsible for cellular functions distinct from CpnA and CpnC. In this study, we obtained two cpnD mutants that were generated via restriction enzyme-mediated integration (REMI) mutagenesis; one in the first exon (cpnD(i291)), and one in the second exon (cpnD(i459)) of the endogenous cpnD gene. Throughout our experiments, we found that cpnD mutants had increased cellular proliferation in both axenic and bacterial cultures. Additionally, we found that cpnD mutants exhibited precocious development and had significantly larger fruiting bodies than the parental cell line. We further investigated the morphology of cpnD mutants and found that they were significantly larger than parental cells and exhibited decreased cell-substrate adhesion. cpnD mutants also had increased activated Ras compared to the parental cell line, along with significantly smaller CVs, a phenotype that was rescued after PI3K inhibition. Finally, we found that GFP-tagged CpnD localizes to the leading edge of both randomly migrating cells and in cells responding to folate. This study is the first to describe copine proteins as having a regulatory function in Ras activation and downstream signaling effects. Additionally, this study further supports our hypothesis that copines act as nonredundant cellular proteins in Dictyostelium to regulate numerous processes.

Chromosome segregation fidelity during meiosis is critical for genome integrity, with aneuploidy causing infertility, miscarriages, and congenital anomalies. In the oocytes of many species, spindle assembly occurs in the absence of centrosomes that normally function as microtubule-organizing centers at the poles. Such acentrosomal spindles are believed to pose significant challenges for accurate chromosome segregation compared to centrosomal organized spindles. Previous work in Drosophila has shown that the chromosomal passenger complex (CPC) is required for acentrosomal spindle assembly. We found that heterochromatin protein-1 (HP1) plays a critical role in regulating CPC localization and spindle assembly. Furthermore, HP1 moves to the microtubules, where it has roles in building a functional spindle and interacts with the CPC to regulate chromosome biorientation. These results indicate that spindle assembly is mediated by multiple interactions between the CPC, HP1, and the chromosomes, and provide insights into the mechanisms that restricts spindle assembly to the chromosomes in Drosophila oocytes.

Although calmodulin is best known as an intracellular calcium sensor, it also possesses calcium-independent functions in unicellular organisms. This is exemplified by the budding yeast S. cerevisiae calmodulin, which binds its essential targets, the pericentrin-like protein Spc110 and type I and V myosins, without needing calcium. Whether such calcium-independent cellular functions are conserved in other yeasts and vertebrates nevertheless remains an open question. Here, we examined the calcium-independent functions of the fission yeast S. pombe calmodulin Cam1 by measuring its intracellular distribution. Using quantitative fluorescence microscopy, we assessed the intracellular localization of two cam1 mutants, where binding of Ca2+ had been compromised by mutations in their EF hands, compared to the wild type protein. Both Cam1-2V and -3V reduced their localization by 90% to the yeast microtubule-organizing center spindle pole bodies (SPB). In contrast, these two mutants did not affect the myosin-dependent localization to the equatorial division plane and to the cell tips. Replacing the endogenous cam1 with cam1-2V decreased the SPB localization of pericentrin Pcp1 by 69%, without changing the localization of either type V or I myosins. Over-expression of Pcp1 rescued the mitotic defects of cam1-2V cells at the restrictive temperature. Surprisingly, the cytokinesis of this cam1 mutant was largely normal. We concluded that fission yeast calmodulin Cam1 depends on Ca2+to be a component of SPBs, suggesting that calcium plays a critical role in the assembly of SPBs.

Mechanosensing involves proteins detecting mechanical changes in the cytoskeleton or at cell adhesion sites. These interactions initiate signaling cascades that produce biochemical effects such as post-translational modifications or cytoskeletal rearrangements. Filamin is a ubiquitous mechanosensing protein that binds actin filaments and senses pulling forces within the cytoskeleton. Drosophila Filamin (Cheerio) is structurally similar to mammalian Filamin, with roles in egg chamber development, embryo cellularization, and integrity of muscle attachment sites and Z discs in Drosophila indirect flight muscles (IFMs). Here we report a potential novel binding partner of Drosophila Filamins: the death-associated protein kinase Drak that functions as a myosin light chain kinase. We found that Drak biochemically bound to an open mutant of Filamin that resembles the mechanically activated form partially bound to wild type Filamin and did not bind to closed mutant of Filamin. The interaction site was mapped to the intrinsically unfolded C-terminal region of Drak. To study the functional role of Drak-Filamin interaction, we studied two developmental events where Drak has been earlier shown to be expressed and where Filamin also functions: early embryonic cellularization and indirect flight muscle development at pupal stages. We found partial colocalization between Drak-GFP and Filamin-mCherry during the initiation of cellularization furrow, and at the time of myotube attachment site maturation in tendon cells. However, functionally we could not show direct correlation between Filamin and Drak. Our studies reveal interesting new expression patterns of Drak during Drosophila development and provide detailed information about Filamin localization during IFM development.

Understanding the functions of maternal effect genes during oocyte growth is essential for elucidating the mechanisms of oogenesis and early embryonic development. However, conventional gene knockout and conditional knockout approaches require extensive breeding and are time-consuming. Here, we present a rapid in vitro gene functional analysis system that combines microinjection of mRNA, siRNA and plasmid DNA into mouse secondary follicles with a two-step oocyte growth culture system. Mouse secondary follicles were subjected to microinjection of mCherry mRNA and subsequently cultured for 15 days to produce fully grown oocytes. mCherry fluorescence persisted throughout the oocyte growth period but declined rapidly after fertilization. Despite minor cellular damage occasionally caused by microinjection, injected follicles developed normally and retained developmental competence. To evaluate the efficiency of gene suppression, we introduced siRNA targeting Dnmt3l, which is abundantly expressed during oocyte growth phase. Although Dnmt3l deficiency is known not to affect oocyte growth, we observed that oocyte growth was maintained normally despite a marked reduction in endogenous Dnmt3l mRNA levels in our knockdown model. These results demonstrate that this method enables efficient manipulation of gene expression specifically during oocyte growth while preserving developmental competence, providing a versatile platform for rapid functional screening of maternal effect genes in vitro.

Elongases are essential enzymes in the biosynthesis of sex pheromones in many lepidopteran species. Together with desaturases, they determine the carbon skeletons of many pheromone precursors, thereby contributing to the production of species-specific chemical signals. However, to date, such fatty acyl elongase gene has not been functionally characterized. The rice leaffolder, Cnaphalocrocis medinalis, utilizes a blend of C18 monounsaturated aldehydes and alcohols as its sex pheromone, implying a critical elongation step from C16 precursors. In this study, we performed pheromone gland transcriptome analysis and identified 45 candidate biosynthetic genes. Functional assays in Nicotiana benthamiana showed that the {Delta}11 desaturase Cmed070400 produces (Z)-11-hexadecenoic acid, which serves as the substrate for elongation. Multiple elongases catalyzed its conversion to (Z)-13-octadecenoic acid, with Cmed092440 showing the highest activity. These findings provide the first experimental evidence for elongase-mediated formation of C18 pheromone precursors in C. medinalis. The identification of a minimal set of functionally active enzymes further enables reconstruction of this pathway in plant systems, offering a basis for sustainable production of pheromone precursors for pest management applications.

Enhancer RNAs (eRNAs) are non-coding transcripts produced at enhancer regions, which appear to be involved in transcriptional regulation. Up to date, these have been primarily investigated using labor-and cost-intensive genomic techniques. However, the precise mechanisms by which eRNA transcription or the eRNA transcripts themselves mediate transcriptional regulation remain unclear. Here, we present a novel experimental approach that allows us to analyze the characteristics of eRNA transcription in fixed and live whole Drosophila melanogaster embryos. We employ the anterior-posterior patterning genes as a model system to investigate the dynamics of eRNA expression, utilizing an imaging-based approach. We combined high-sensitivity fluorescence in situ hybridization (FISH) chain reaction (HCR) with high-resolution confocal microscopy to detect eRNA and mRNA molecules. Through this experimental assay, we identified foci of elevated transcriptional activity that generate eRNA transcripts correlated with mRNA production at the same gene locus. We could show that this eRNA transcription is independent of promoter activity. Additionally, we demonstrate that insulators can influence eRNA transcription, resulting in loss of eRNA transcription. Moreover, we observe that eRNAs can originate both within classical enhancer regions and outside of them, including from foreign bacterial sequences when these are placed near enhancer sequences, underscoring the strong influence of local regulatory context on eRNA initiation. In live embryos using MS2-MCP live imaging, our analysis of insulators showed a modest reduction in mRNA burst intensity accompanied by a slight increase in burst frequency. Overall, our imaging-based approach offers a novel platform for dissecting enhancer-eRNA interactions and could be adapted for wider applications.

The diversity of the brown frog genus Rana may be underestimated as the high similarity of morphological characters. A new species belonging to the genus Rana is delineated based on eight specimens obtained from the Tianma National Nature Reserve, Jinzhai County, Luan City, Anhui Province, China. The phylogenetic analysis based on three mitochondrial genes (12S, ND2, and Cyt b) and one nuclear gene (BDNF) showed that the new species formed an independent clade closely related to R. culainensis and received strong support. In addition, morphological differentiation confirmed the phylogenetic results, and both supported the validity of a new species (Rana tianmaensis sp. nov.) in the R. japonica species group. The discovery of this new species enhances peoples understanding of the biodiversity of Rana and can provide important foundational data for scientific decision-making on protected area construction, ecological conservation, and species diversity. With the inclusion of newly described species in this study, the distribution of Rana genus in China now includes 31 recognized species.

The neurosteroid allopregnanolone is a positive allosteric modulator of GABA(A) receptors, which has proved beneficial in the treatment of major depressive disorder and epilepsies. It also has a role in treating the mood swings that are associated with fluctuations in its level during the menstrual cycle. Nonetheless, a subset of women do not tolerate high levels of allopregnanolone. Iso-allopregnanolone, a negative allosteric modulator, as well as synthetic steroid antagonists are used to treat such conditions. However, steroid-based medications are difficult to deliver and their specificity of action can be unclear. Recently introduced novel nonsteroidal agents that, like iso-allopregnanolone, can reverse the action of positive allosteric modulators without changing the positive action of GABA, might provide an alternative. We surveyed a number of them on human 1{beta}3{delta} GABAARs using a [3H]muscimol binding assay. A 6-membered ring spiro-hydantoin, DKD99, allosterically reversed the positive allosteric action of allopregnanolone over a wide concentration range (6 to 1,000 nM). DKD99 shifted allopregnanolones modulation curve 10-fold to the right. Furthermore, it has a much lower affinity when exerting similar actions on 1{beta}3{gamma}2 receptors. Agents such as this have utility for elucidating underlying mechanisms and may offer an alternative pathway for the development of nonsteroidal therapies against the positive allosteric modulatory actions of neurosteroids.

In mammals, silent state of one of the X-chromosomes in female balance the X-dosage between sexes. In parallel, X to autosome imbalance due to monoallelic expression of X-linked genes relative to biallelic autosomal genes, is primarily compensated through the X-chromosome upregulation (XCU). It has been demonstrated that X-chromosome inactivation (XCI) and XCU coincides during embryogenesis, however, XCU is not global and it occurs in a gene-specific manner. The underlying mechanistic aspects of such specificity of XCU remain unknown. Here, we provide systematic and comparative analysis across eutherians (mouse, human and pig) and metatherian (opossum) embryogenesis to determine if evolutionary origins shape the XCU. Intriguingly, we show that while evolutionary older X-linked genes (predating mammalian divergence) undergo robust XCU consistently across developmental stages, younger mammalianLJorigin genes do not. Similarly, the eutherian X-linked genes conserved in metatherian X (X-ortholog) undergo robust XCU, whereas genes orthologus to metatherian autosome (Auto-ortholog) exhibit weaker pattern of XCU. Further, strata-wise comparison revealed that genes in older XLJchromosome strata (1-2) consistently undergo upregulation, whereas strata 3-4 genes do not. Importantly, we show that different evolutionary classes of X-linked genes, which undergo robust XCU, are often enriched with active chromatin marks (H3K36me3, H3K27ac and H3K4me1) relative to the autosome, suggesting that chromatin state mediate the XCU. Moreover, we show that often active-marks enrichment correlates with differential XCU dynamics of different class of genes. Taken together, our study provides significant insight into the evolutionary dynamics of XCU and underlying mechanistic framework.

Nucleobindin 1 (NUCB1) is a multifunctional conserved protein located in Golgi luminal, nucleus, extracellular and cytosolic pools. NUCB1 is multidomain protein comprised of a signal peptide, a DNA-binding domain, a leucine zipper and Ca2+ -binding domain. The multiple domains and localization of NUCB1 potentiates its interactions with various partners, such as DNA, Gi3 protein, cyclooxygenase 2, LRP10 and RNA suggests its importance in the regulation of many cellular events. We revealed that NUCB1 contains three RNA-binding regions and able to interact with two RNA fragments. It was suggested possible variants of the participation of NUCB1 in the interaction of the two partially complementary RNAs. The RNA-binding properties of the NUCB1 were also confirmed in vivo experiments.

MicroRNAs (miRNAs) play essential roles in the posttranscriptional regulation of gene expression in organisms. In the process of synthesizing mature miRNAs from miRNA precursors, the miRNA precursors are cleaved via Dicer at their loop structure, after which the miRNA precursors become mature and regulate transcription. However, the consequences of altering the loop sequence are not fully understood. The silkworm Bombyx mori is a lepidopteran insect with many genetic strains. We identified a mutant of the miRNA miR-3260 whose the part of the loop structure was lacking in a silkworm strain with translucent larval skin. Here, we aimed to analyze the role of wild-type miR-3260 and the influence of the mutation of the loop structure in B. mori. First, we identified the genomic region responsible for the translucent larval skin phenotype and determined that the mutated miR-3260 nucleotide sequences. Then, we predicted the binding partners of wild-type miR-3260 using the RNA hybrid tool and found two juvenile hormone (JH)-related genes as targets of wild-type miR-3260. Next, we assessed the relationships between miR-3260 and JH and found that miR-3260 was highly expressed in the Corpora allata and its expression responded to JH treatment. Meanwhile, miR-3260 mimic and inhibitor did not induce the typical phenotypes associated with JH in B. mori. Then, we compared the dicing products from wild-type and mutant miR-3260 precursors and observed that neither form underwent Dicer-mediated cleavage when the loop structure was altered. These results suggest that loop mutations in the miR-3260 precursor may not influence dicing activity, consistent with the lack of observable phenotypic effects.

B-cell leukemia/lymphoma 11B (BCL11B), despite its name, is a key regulator of T-cell development, specification, and T-cell malignancies. BCL11B contains a bipartite DNA binding domain composed of two C2H2 zinc finger arrays: low-affinity ZF2-3 and high affinity ZF4-6. These arrays function as homotypic modules that recognize similar six-nucleotide motifs, TG(O_SCPLOWNC_SCPLOW)CC(O_SCPLOWCC_SCPLOWO_SCPCAP/C_SCPCAPO_SCPLOWTC_SCPLOWO_SCPCAP/C_SCPCAPO_SCPLOWAC_SCPLOW), as seven of the eight DNA base-contacting residues are conserved between them. The most conserved interactions involve GG dinucleotides, contacted by arginine and lysine residues at key base-interacting positions in ZF3 and ZF5. The two ZF arrays are connected by a long [~]300-residue linker that provides flexibility in how the arrays engage DNA, allowing ZF2-3 and ZF4-6 binding to the same or opposite strands with variable orientation, spacing and positioning along the DNA. This extended linker is enriched in serine/threonine, acidic residues (aspartate/glutamate), and structural residues (glycine/proline), providing additional layers of transcriptional regulation possibly through post-translational modification, electrostatic modulation, and/or condensate formation. We also examined six missense mutations in base-interacting residues, that are associated with neurodevelopmental disorders. Substitutions replacing bulky, positively charged arginine or lysine with smaller or hydrophobic residues likely reduce DNA-binding affinity and/or specificity, whereas substitutions between asparagine and lysine may alter base recognition preferences.

Histone lactylation is a recently identified histone post-translational modification (PTM) that links energy metabolism to chromatin regulation. Although histone lactylation has been implicated in transcriptional activation, its function in meiotic chromatin remains unclear. Previously, we identified enrichment of multiple histone lactylation marks within the meiotic karyosome, a highly condensed and transcriptionally repressive chromatin structure formed in Drosophila oocytes. Here, through an RNAi-based screen, we identified the CBP family protein dCBP as a regulator of histone lactylation in the karyosome. Germline-specific knockdown of dCBP preferentially reduced histone lactylation, including H4K8 lactylation, and caused premature disruption of the synaptonemal complex, abnormal egg chamber development with excess nurse cells, reduced egg production, and decreased embryonic viability. Corresponding histone acetylation marks were comparatively less affected than histone lactylation by dCBP knockdown. Together, our findings provide evidence that dCBP-mediated histone lactylation contributes to meiotic chromosome maintenance and suggest a potential link between energy metabolism and meiotic chromatin regulation.

The Caenorhabditis elegans AWC olfactory neuron pair specifies asymmetric subtypes, AWCOFF and AWCON, through stochastic and coordinated cell signaling events. UNC-104/kinesin-3 (KIF1A) and UNC-116/kinesin-1 motor proteins act in the AWCON cell to regulate the synaptic localization of the TIR-1/SARM1-assembled calcium signaling complex in the AWCOFF cell to promote AWCOFF. However, the molecular mechanism in the AWCON cell that acts non-cell autonomously to control synaptic TIR-1 calcium signaling to promote AWCOFF remains unclear. Here, we show that JIP-1, a conserved c-Jun N-terminal kinase (JNK)-interacting protein 1, mediates the synaptic localization of TIR-1 in the AWC axon to specify the AWCOFF subtype. A jip-1 loss-of-function mutant, identified from an unbiased forward genetic screen, has reduced localization of TIR-1 at synapses in the AWC axon and accumulation of TIR-1 in the AWC cell body. jip-1 mutants significantly enhance the 2AWCON phenotype of a hypomorphic tir-1 mutant. JIP-1, like UNC-104 and UNC-116, mainly acts non-cell autonomously in AWCON to specify the AWCOFF subtype. Our findings provide mechanistic insights into how cell-specific Ca2+ signaling proteins, such as TIR-1, target synaptic regions via intercellular signaling to promote neuronal diversification.

Transcriptomic analyses are widely used to elucidate the molecular mechanisms driving gametogenesis and reproduction in fish, yet their accuracy depends heavily on appropriate normalization of gene expression data. Conventional approaches that rely on single or multiple reference genes are problematic during teleost oogenesis, as profound structural and physiological remodeling of the ovary challenges the assumption that commonly used reference transcripts remain stable. In this study, we assessed by qPCR the transcriptional variability of four widely used reference genes (actb, ef-1, gapdh, and 18S rRNA) throughout the oogenic cycle of the thicklip grey mullet (Chelon labrosus), using geNorm and NormFinder analyses, and we additionally evaluated total cDNA concentration as an alternative normalization factor. To examine the performance and interpretive consequences of each normalization strategy, we compared expression patterns of key steroidogenic genes (star, cyp19a1a, and cyp11b) normalized by individual reference genes, combinations of reference genes, or total cDNA concentration. All evaluated reference genes displayed notable transcriptional variability across oogenesis, confirming their limited suitability as sole internal controls. In contrast, normalization approaches integrating multiple reference genes and/or total cDNA concentration consistently provided greater stability and more reliable biological interpretation. These results support a refined and more robust normalization framework for transcriptional analyses in fish ovaries, particularly during stages of extensive tissue remodeling. Our findings demonstrate cDNA-based normalization is straightforward, rapid, and easy to implement across laboratories, providing a practical alternative for achieving accurate, reproducible transcript quantification in fish ovary studies.

BackgroundDynamic chromatin behavior, which is related to chromatin accessibility, plays a critical role in various genome DNA functions such as RNA transcription and DNA replication/repair. Previous studies using highly synchronized cells showed that average local chromatin motion, captured by single-nucleosome imaging and tracking on a second time scale, remained almost constant throughout G1, S, and G2 phases in living human cells, although possible effects of prolonged drug treatments for cell-cycle synchronization could not be excluded. ResultsTo avoid possible effects of prolonged drug treatment, we combined single-nucleosome imaging with Fucci probes to visualize cell-cycle progression through G1, S, and G2. Using HeLa and HCT116 cells expressing H2B-HaloTag and Fucci probes, we found that local nucleosome motion remained similar on average throughout interphase, except for elevated motion in early G1. Transcription inhibition similarly increased nucleosome motion throughout interphase. Local nucleosome motion also increased following replication stress or DNA damage. ConclusionOur findings suggest that near-constant chromatin motion supports housekeeping functions under similar physical conditions during interphase. Our findings also suggest that cells can transiently change chromatin motion to perform ad hoc tasks in response to signals from inside and outside the cell, such as DNA damage.