Biology subjects

Deng, D.

Publications and source records attributed to Deng, D..

At least 37 records · Page 2Linked to original sources

bioRxiv2022

Oncogenic context shapes the fitness landscape of tumor suppression

Tumors acquire alterations in oncogenes and tumor suppressor genes in an adaptive walk through the fitness landscape of tumorigenesis. However, the features of this landscape remain poorly understood and cannot be revealed by human cancer genotyping alone. Here, we use a multiplexed, autochthonous mouse platform to model and quantify the initiation and growth of more than one hundred genotypes of lung tumors across four oncogenic contexts: KRAS G12D, KRAS G12C, BRAF V600E, and EGFR L858R. The resulting fitness landscape is rugged (the effect of tumor suppressor inactivation often switches between beneficial and deleterious depending on the oncogenic context), shows no evidence of diminishing-returns epistasis within variants of the same oncogene, and is inconsistent with expectations of a simple linear signaling relationship among these three oncogenes. Our findings suggest that tumor suppressor effects are strongly context-specific, which limits the set of evolutionary paths that can be taken through the fitness landscape.

cancer biology↗

bioRxiv2022

Effects of antennal segments defects on blood-sucking behavior in Aedes albopictus

After mating, female mosquitoes need a blood meal to promote the reproductive process. The blood-feeding transmits extremely harmful infections including malaria, yellow fever, dengue fever, and other arboviruses, making mosquitoes one of the most harmful creatures to human health. The selection and localization of the host by mosquitoes mainly depends on the trace chemical cues emitted by the host into the environment, and the sense of smell is the main way to perceive these trace chemical cues. However, the knowledge of the olfactory mechanism is not enough to meet the needs of mosquito control. Unlike previous studies that focused on the olfactory receptor recognition spectrum to reveal the olfactory mechanism of mosquito host localization. In this paper, we proposed that artificial defects in mosquito antennal flagellomeres may affect their blood-feeding behavior, and through rationally designed behavioral experiments, we found that the 6th and 7th flagellomeres on Aedes albopictus antenna are important in the olfactory detection of host searching. Meanwhile, the morphology and distribution of sensilla on each antenna flagellomere were also analyzed and discussed in this paper.

animal behavior and cognition↗

bioRxiv2021

Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis

Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen Listeria monocytogenes encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD+ regeneration, but this could be specifically reversed by heterologous expression of a water-forming NADH oxidase (NOX). NOX expression fully rescued intracellular growth defects and increased L. monocytogenes loads >1,000-fold in a mouse infection model. Consistent with NAD+ regeneration maintaining L. monocytogenes viability and enabling immune evasion, a respiration-deficient strain exhibited elevated bacteriolysis within the host cytosol and NOX rescued this phenotype. These studies show that NAD+ regeneration, rather than oxidative phosphorylation, represents the primary role of L. monocytogenes respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.

microbiology↗

bioRxiv2021

A ROS-Ca2+ signalling pathway identified from a chemical screen for modifiers of sugar-activated circadian gene expression.

Sugars are essential metabolites for energy and anabolism that can also act as signals to regulate plant physiology and development. Experimental tools to disrupt major sugar signalling pathways are limited. We have performed a chemical screen for modifiers of activation of circadian gene expression by sugars to discover pharmacological tools to investigate and manipulate plant sugar signalling. Using a library of commercially available bioactive compounds, we identified 75 confident hits that modified the response of a circadian luciferase reporter to sucrose in dark-adapted seedlings. We validated the transcriptional effect on a subset of the hits and measured their effects on a range of sugar-dependent phenotypes for 13 of these chemicals. Chemicals were identified that appear to influence known and unknown sugar signalling pathways. Pentamidine isethionate (PI) was identified as a modifier of a sugar-activated Ca2+ signal that acts downstream of superoxide in a metabolic signalling pathway affecting circadian rhythms, primary metabolism and plant growth. Our data provide a resource of new experimental tools to manipulate plant sugar signalling and identify novel components of these pathways.

plant biology↗

bioRxiv2021

Extrasynaptic NMDA receptors bidirectionally modulate intrinsic excitability of inhibitory neurons

The NMDA subtype glutamate receptors (NMDARs) play important roles in both physiological and pathological processes in the brain. Comparing to their critical roles in synaptic modifications and excitotoxicity in the excitatory neurons, much less is understood about the functional contributions of NMDARs to the inhibitory/GABAergic neurons. By using selective NMDAR inhibitors and potentiators, we here show that NMDARs bi-directionally modulate the intrinsic excitability (defined as spontaneous/evoked spiking activity and EPSP-spike coupling) in the inhibitory/GABAergic neurons. This modulation depends on GluN2C/2D-but not GluN2A/2B-containing NMDARs. We further show that NMDAR modulator EU1794-4 mostly enhances extrasynaptic NMDAR activity, and by using it we demonstrate a significant contribution of extrasynaptic NMDARs to the modulation of intrinsic excitability in the inhibitory neurons. Altogether, this bidirectional modulation of intrinsic excitability reveals a previously less appreciated importance of NMDARs in the second-to-second functioning of inhibitory/GABAergic neurons.

neuroscience↗

bioRxiv2021

The genomic context for aflatoxin B1-degrading Pseudomonas strains

The whole genomes of three strains were sequenced and annotated. COG (Clusters of Orthologous Groups) and GO (Gene Ontology) annotations of the protein-coding genes from three strains show a conservation of genome-wide protein functions in genus Pseudomonas. However, the AFB1-degrading strains HAI2 and HT3 harbor much more genes belonged to the pathway of xenobiotics biodegradation and metabolism than non-degrading strain 48. Besides, the enzyme families potentially involved in the AFB1 degradation of bacteria are more abundant in the two AFB1-degrading strains. A pan-genome profile was then formed by comparing the genomes against other reference genomes of the corresponding Pseudomonas species. Accordingly, a total of 1,528 genes were found to be specific in AFB1-degrading strains, and 65 genes of them are related to oxidoreductase activity.

microbiology↗

bioRxiv2021

Cryo-EM structures of human TMEM120A and TMEM120B

TMEM120A (Transmembrane protein 120A) was recently identified as a mechanical pain sensing ion channel named as TACAN, while its homologue TMEM120B has no mechanosensing property1. Here, we report the cryo-EM structures of both human TMEM120A and TMEM120B. The two structures share the same dimeric assembly, mediated by extensive interactions through the transmembrane domain (TMD) and the N-terminal coiled coil domain (CCD). However, the nearly identical structures cannot provide clues for the difference in mechanosensing between TMEM120A and TMEM120B. Although TMEM120A could mediate conducting currents in a bilayer system, it does not mediate mechanical-induced currents in a heterologous expression system, suggesting TMEM120A is unlikely a mechanosensing channel. Instead, the TMDs of TMEM120A and TMEM120B resemble the structure of a fatty acid elongase, ELOVL7, indicating their potential role of an enzyme in lipid metabolism.

biophysics↗

bioRxiv2020

CIGAR-seq, a CRISPR/Cas-based method for unbiased screening of novel mRNA modification regulators

Cellular RNA is decorated with over 170 types of chemical modifications. Many modifications in mRNA, including m6A and m5C, have been associated with critical cellular functions under physiological and/or pathological conditions. To understand the biological functions of these modifications, it is vital to identify the regulators that modulate the modification rate. However, a high-throughput method for unbiased screening of these regulators is so far lacking. Here, we report such a method combining pooled CRISPR screen and reporters with RNA modification readout, termed CRISPR integrated gRNA and reporter sequencing (CIGAR-seq). Using CIGAR-seq, we discovered NSUN6 as a novel mRNA m5C methyltransferase. Subsequent mRNA bisulfite sequencing in HAP1 cells without or with NSUN6 and/or NSUN2 knockout showed that NSUN6 and NSUN2 worked on non-overlapping subsets of mRNA m5C sites, and together contributed to almost all the m5C modification in mRNA. Finally, using m1A as an example, we demonstrated that CIGAR-seq can be easily adapted for identifying regulators of other mRNA modification.

molecular biology↗

bioRxiv2020

New evidence concerning the genome designations of the AC(DC) tetraploid Avena species

The tetraploid Avena species in the section Pachycarpa Baum, including A. insularis, A. maroccana, and A. murphyi, are thought to be involved in the evolution of hexaploid oats; however, their genome designations are still being debated. Repetitive DNA sequences play an important role in genome structuring and evolution, so understanding the chromosomal organization and distribution of these sequences in Avena species could provide valuable information concerning genome evolution in this genus. In this study, the chromosomal organizations and distributions of six repetitive DNA sequences (including three SSR motifs (TTC, AAC, CAG), one 5S rRNA gene fragment, and two oat A and C genome specific repeats) were investigated using non-denaturing fluorescence in situ hybridization (ND-FISH) in the three tetraploid species mentioned above and in two hexaploid oat species. Preferential distribution of the SSRs in centromeric regions was seen in the A and D genomes, whereas few signals were detected in the C genomes. Some intergenomic translocations were observed in the tetraploids; such translocations were also detected between the C and D genomes in the hexaploids. These results provide robust evidence for the presence of the D genome in all three tetraploids, strongly suggesting that the genomic constitution of these species is DC and not AC, as had been thought previously.

genetics↗

bioRxiv2020

Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism

Steroid hormones are essential in stress response, immune system regulation, and reproduction in mammals. Steroids with 3-oxo-{Delta}4 structure, such as testosterone, androstenedione and progesterone, could be catalyzed by steroid 5-reductases (SRD5As) to generate their corresponding 3-oxo-5 steroids, which are essential for multiple physiological and pathological processes. Abnormal activities of SRD5As will lead to benign prostatic hyperplasia, alopecia, prostatic cancer or infertility due to the poor quality of sperms. However, the detailed reduction mechanisms of SRD5As remain elusive. Here we report the crystal structure of PbSRD5A, which shares 60.6% and 51.5% sequence similarities with human SRD5A1 and -2 respectively, from Proteobacteria bacterium in complex with the cofactor NADPH at 2.0 [A] resolution. PbSRD5A exists as a monomer comprised of seven transmembrane segments (TMs). The TM1-4 enclose a hydrophobic cavity for steroids substrates binding, whereas TM5-7 coordinate with cofactor NADPH through extensive hydrogen bonds network. Homology-based structural models of HsSRD5A1 and -2, together with extensive biochemical characterizations, for the first time unveiled the substrate recognition of SRD5As and provide an important framework for further understanding of the mechanism of NADPH mediated steroids 3-oxo-{Delta}4 reduction. Based on these analyses, the design of therapeutic molecules targeting SRD5As with improved specificity and therapeutic efficacy would be possible. One Sentence SummaryStructural and biochemical characterizations decipher the evolutionarily conserved mechanism in steroid 5-reductases catalyzing NADPH mediated steroids reduction.

biochemistry↗

bioRxiv2020

ActuAtor, a molecular tool for generating force in living cells: Controlled deformation of intracellular structures

Mechanical force underlies fundamental cell functions such as division, migration and differentiation. While physical probes and devices revealed cellular mechano-responses, how force is translated inside cells to exert output functions remains largely unknown, due to the limited techniques to manipulate force intracellularly. By engineering an ActA protein, an actin nucleation promoting factor derived from Listeria monocytogenes, and implementing this in protein dimerization paradigms, we developed a molecular tool termed ActuAtor, with which actin polymerization can be triggered at intended subcellular locations to generate constrictive force in a rapidly inducible manner. The ActuAtor operation led to striking deformation of target intracellular structures including mitochondria, Golgi apparatus, nucleus, and non-membrane-bound RNA granules. Based on functional analysis before and after organelle deformation, we found the form-function relationship of mitochondria to be generally marginal. The modular design and genetically-encoded nature enable wide applications of ActuAtor for studies of intracellular mechanobiology processes.

cell biology↗

bioRxiv2020

Chidamide decreases c-MET mRNA methylation and in turn increases the sensitivity of non-small cell lung cancer to crizotinib

IntroductionCrizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) with ALK mutations. Although c-MET is frequently overexpressed in 35-72% of NSCLC, most NSCLCs are primarily resistant to crizotinib treatment. MethodA set of NSCLC cell lines were used to test the effect of chidamide on the crizotinib sensitivity in vitro and in vivo. Relationships between the synergistic effect of chidamide and c-MET expression and RNA methylation were systemically studied with a battery of molecular biological assays. ResultsWe found for the first time that chidamide could increase the crizotinib sensitivity of a set of ALK mutation-free NSCLC cell lines, especially those with high levels of c-MET expression. Notably, chidamide could not increase the crizotinib sensitivity of NSCLC cells cultured in serum-free medium without hepatocyte growth factor (HGF; a c-MET ligand). In contrast, the addition of HGF into the serum-/HGF-free medium could restore the synergistic effect of chidamide. Moreover, the synergistic effect of chidamide could also be abolished either by treatment with c-MET antibody or siRNA-knockdown of c-MET expression. While cells with low or no c-MET expression were primarily resistant to chidamide-crizotinib cotreatment, enforced c-MET overexpression could increase the sensitivity of these cells to chidamide-crizotinib cotreatment. Furthermore, chidamide could decrease c-MET expression by inhibiting mRNA N6-methyladenosine (m6A) modification through the downregulation of METTL3 and WTAP expression. Chidamide-crizotinib cotreatment significantly suppressed the activity of c-MET downstream molecules. Conclusionchidamide downregulated c-MET expression by decreasing its mRNA m6A methylation, subsequently increasing the crizotinib sensitivity of NSCLC cells in a c-MET-/HGF-dependent manner. GRAPHIC SUMMARY O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/012971v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@5a81d4org.highwire.dtl.DTLVardef@19f1forg.highwire.dtl.DTLVardef@75d74forg.highwire.dtl.DTLVardef@8a9f77_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2020

T606-phosphorylated Kaiso interacting with 14-3-3 and p120ctn is sequestered in the cytoplasm of human cells

It is well known that Kaiso protein encoded by ZBTB33 gene is a transcription repressor and that Kaiso-P120ctn interaction increases the shift of Kaiso from the nucleus into the cytoplasm. However, the regulatory mechanisms of Kaiso compartmentalization are far from clear. Here, we reported that AKT1 could phosphorylate 606-threonine residue (T606) within the RSSTIP motif of Kaiso in the cytoplasm. The T606-phosphorylated Kaiso (pT606-Kaiso) could directly bind to 14-3-3 family proteins and the depletion of T606 phosphorylation by T606A mutation abolished most of the Kaiso-14-3-3 binding. In addition, the Kaiso-P120ctn interaction was essential for the pT606-Kaiso accumulation in the cytoplasm. Notably, enforced 14-3-3{sigma} (SFN) overexpression could increase the pT606-Kaiso accumulation in the cytoplasm and de-repress the transcription of Kaiso target gene CDH1. Decreased amounts of both pT606-Kaiso and CDH1 proteins were frequently observed in human gastric cancer tissues relative to paired normal controls. The mRNA levels of 14-3-3{sigma} and Kaiso target gene CDH1 were positively and significantly correlated with each other in bioinformatics analyses using publicly available RNA-seq datasets for human normal tissues (n=11688, r=0.60, p<0.001) in the GTEx project and for cancer cell lines (n=1156, r=0.41, p<0.001) in the CCLE project. Furthermore, Kaiso T606A mutant (unable to be phosphorylated) significantly increased the migration and invasion of cancer cells in vitro as well as boosted the growth of these cells in vivo. In conclusion, Kaiso could be phosphorylated by AKT1 at the T606 and the pT606-Kaiso accumulates in the cytoplasm through binding to 14-3-3/P120ctn that de-represses the expression of Kaiso target gene CDH1 in normal tissues. Decreased Kaiso phosphorylation may contribute to the development of gastrointestinal cancer. The status of Kaiso phosphorylation is a determinant factor for the role of Kaiso in the development of cancer.

molecular biology↗

bioRxiv2020

A novel fibrinogen gamma-chain mutation, p. γAla327Val, causes structural abnormality of D region and ultimately leads to congenital dysfibrinogenemia

Congenital dysfibrinogenemia (CD) is a coagulation disorder caused by mutations in the fibrinogen gene, which result in abnormal fibrinogen function. Many studies have confirmed that over half of dysfibrinogenemia cases are asymptomatic. In this study, we aimed to investigate the pathogenesis of CD caused by {gamma} Ala327Val heterozygous mutation, a new mutation, by studying fibrinogen function. Blood samples of patients were collected and the coagulation function, fibrinogen (Fg) aggregation test, fibrin clot lysis test, and SDS-PAGE were performed. Coagulation was monitored using a thromboelastometer, and the fibrin clot network structure was observed by scanning electron microscopy. The effect of the mutation on fibrinogen structure and function was predicted by molecular modeling. The fibrinogen activity concentration in patients with CD was significantly lower than that in healthy individuals. Thromboelastography showed that the K value of patients with CD was higher than that for healthy individuals. The Angle values were also decreased. The function of fibrinogen in patients with CD was low. Compared to fibrinogen from healthy individuals, fibrin size was different, the fiber network structure was loose, the pore size was increased, and the fiber branch nodes were increased for fibrinogen isolated from the proband. The {gamma} Ala327Val mutation led to changes in the structure of fibrinogen D region, affecting its structural stability. Ala327Val heterozygous missense mutation in exon 8 of FGG gene {gamma}-chain thus leads to abnormal fibrinogen structure and impairs the aggregation function of fibrinogen. This mutation is reported here for the first time.

molecular biology↗

bioRxiv2019

P16 methylation increases the sensitivity of cancer cells to the CDK4/6 inhibitor palbociclib

The P16 (CDKN2Aink4a) gene is an endogenous CDK4/6 inhibitor. Palbociclib (PD0332991) is an anti-CDK4/6 chemical for cancer treatment. P16 is most frequently inactivated by copy number deletion and DNA methylation in cancers. It is well known that cancer cells with P16 deletion are more sensitive to palbociclib than those without. However, whether P16 methylation is related to palbociclib sensitivity is not known. By analyzing public pharmacogenomic datasets, we found that the IC50 of palbociclib in cancer cell lines (n=522) was positively correlated with both the P16 expression level and P16 gene copy number. Our experimental results further showed that cancer cell lines with P16 methylation were more sensitive to palbociclib than those without. To determine whether P16 methylation directly increased the sensitivity of cancer cells to palbociclib, we induced P16 methylation in the lung cancer cell lines H661 and HCC827 and the gastric cancer cell line BGC823 via an engineered P16-specific DNA methyltransferase (P16-Dnmt) and found that the sensitivity of these cells to palbociclib was significantly increased. The survival rate of P16-Dnmt cells was significantly lower than that of vector control cells 48 hrs post treatment with palbociclib (10 M). Notably, palbociclib treatment also selectively inhibited the proliferation of the P16-methylated subpopulation of P16-Dnmt cells, further indicating that P16 methylation can increase the sensitivity of cells to this CDK4/6 inhibitor. These results were confirmed in an animal experiment. In conclusion, inactivation of the P16 gene by DNA methylation can increase the sensitivity of cancer cells to palbociclib.

pharmacology and toxicology↗

bioRxiv2019

Soil and vegetation conditions changes following the different sand dune restoration measures on the Zoige Plateau

Restoration of alpine sand dunes has been increasingly attracting the attention of ecologists due to their difficulty and importance among the mountain-river-forest-farmland-lake-grass system (referred as meta-ecosystem) restoration. Alpine sand dunes are suffered from unstable soil and lack of plants. Efficient restoration measures are vital to guide the sand dune restoration. Whether the engineering materials co-applied with seeding could achieve considerable restoration in such areas? Here, sandbag and wicker as environmental friendly materials combined with Elymus nutans seeding were implemented on the Zoige Plateau sand dune, comparing with the control treatment that only seeding. We assessed the topsoil conditions by sampled the surface soil and measured the water capacity and nutrients. We also utilized interspecific relationship and population niche to analyse the plant community structure variances among different restoration measures. Results showed that the soil conditions got clearly improved in sandbag area than that in wicker area when compared with that in control area. The community in control area was the least structured, while the species showed the closest related in sandbag area. In addition, average population niche overlap showed a control (0.26) < wicker (0.32) < sandbag (0.39) ranking. Thus, we suggested that sandbag or wicker co-applied with indigenous grass seeding is a practical and quick restoration approach in alpine sand dunes, and the sandbag may surpasses the wicker. Moreover, soil amending measures including nutrient improvement, and microbial fertilizer addition may further accelerate sand dune restoration.

ecology↗

bioRxiv2018

Hydroxymethylated-P16 Allele Is Transcription-Inactive

Background5-Methylcytosine can be oxidized into 5-hydroxymethylcytosine (5hmC) in the genome. Methylated-P16 (P16M) can be oxidized into completely hydroxymethylated-P16 (P16H) in human cancer and precancer cells. The aim of this study is to investigate the biological function of P16H.\n\nMethodsTrue P16M and P16H were analyzed using bisulfite/TAB-based assays. A ZFP-based P16-specific dioxygenase (P16-TET) was constructed and used to induce P16H. Cell proliferation and migration were determined with a series of biological analyses.\n\nResults(A) The 5hmCs were enriched in the antisense-strand of the P16 exon-1 in HCT116 and AGS cells containing methylated-P16 alleles (P16M). (B) P16-TET induced both P16H and P16 demethylation in H1299 and AGS cells and reactivated P16 expression. Notably, P16H was only detectable in the sorted P16-TET H1299 and AGS cells that did not show P16 expression. (C) P16-TET significantly inhibited the xenograft growth derived from H1299 cells in NOD-SCID mice, but did not inhibit the growth of P16-deleted A549 control cells. P16-siRNA knockdown could rescue P16-TET-inhibited cell migration.\n\nConclusionHydroxymethylated P16 alleles are transcriptionally inactive.\n\nAUTHOR SUMMARYIt is well known that 5-methylcytosine (5mC) in genomic DNA of mammalian cells can be oxidized into 5-hydroxymethylcytosine (5hmC) and other derivates by DNA dioxygenase TETs. While conversion of 5mC to 5hmC plays an important role in active DNA demethylation through further oxidations, a certain proportion of 5hmCs remain in the genome. Although it is supposed that occurrence of 5hmCs may contribute to the flexibility of chromatin and the protection of the bivalent promoters from hypermethylation, the direct effect of 5hmCs on gene transcription is unknown. In the present study, we engineered a zinc-finger protein-based P16-specific DNA dioxygenase and used it to induce P16 hydroxymethylation and demethylation in cancer cells. Our results demonstrate, for the first time, that the hydroxymethylated P16 alleles retain transcriptionally inactive. This is supported by our recent findings that mRNAs are always transcribed only from the unmethylated P16 strands, but not from the hydroxymethylated/methylated strands in HCT116 cells, and that the risks for malignant transformation are similar for patients with the P16 methylation-positive oral epithelial dysplasia with and without P16 hydroxymethylation in a prospective study.

molecular biology↗

bioRxiv2018

Effects of P16 DNA Methylation on Proliferation, Senescence, and Lifespan of Human Fibroblasts

The aim is to study the effects of P16 DNA methylation on lifespan of normal cells. An expression-controllable pTRIPZ vector expressing P26-specific zinc finger binding protein-based methyltransferase (P16-Dnmt) was used to induce P16 methylation in primary CCD-I8C0 fibroblasts via stable transfection. Long-term dynamic IncuCyte analysis showed that CCD-I8C0 fibroblasts expressing baseline P16-Dnmt continued proliferating until passage-26 in the 53th post-transfection week, while vector control cells stopped proliferating at passage-6 and completely died 2 weeks later. The proliferation rate of baseline P16-Dnmt cells was significantly higher than that of vector control cells. The proportion of P-galactosidase-positive staining cells was significantly decreased in baseline P16-Dnmt cells compared to vector control cells. The P16 expression was lost in baseline P16-Dnmt cells at and after passage-6. The average telomere length in baseline P16-Dnmt cells also gradually decreased. In conclusion, P16 methylation could prevent senescence, promote proliferation, and expand lifespan of human fibroblasts, which may play a role in cancer development.\n\nSummaryA zinc finger protein-based DNA methyltransferase (P16-Dnmt) expressed at the baseline level could specifically methylate P16 promoter CpG islands. P16 methylation induced by baseline P16-Dnmt could significantly prevent senescence, promote proliferation, and expand lifespan of primary human fibroblasts.

cell biology↗