Publications by authors named "Gengqiang Xie"

12 Publications

  • Page 1 of 1

Nuclear mechanosensing: mechanism and consequences of a nuclear rupture.

Mutat Res 2020 May - Dec;821:111717. Epub 2020 Aug 5.

Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, United States. Electronic address:

The physical connections between the cytoskeletal system and the nucleus provide a route for the nucleus to sense the mechanical stress both inside and outside of the cell. Failure to withstand such stress leads to nuclear rupture, which is observed in human diseases. In this review, we will go through the recent findings and our current understandings of nuclear rupture. Starting with the triggers of nuclear rupture, including the aberrant nuclear lamina composition and the elevated actomyosin contractility. We will also discuss the role of ESCRT-III in nuclear rupture repair and the biological consequences of nuclear rupture, including the negative impacts on cellular compartmentalization, DNA damage, and cellular differentiation. Recent studies on nuclear rupture provide further insights into the direct mechanistic link between nuclear rupture and several pathological conditions. Such knowledge can guide us in developing potential therapeutic solutions for the patients.
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http://dx.doi.org/10.1016/j.mrfmmm.2020.111717DOI Listing
December 2020

A single-cell atlas of adult Drosophila ovary identifies transcriptional programs and somatic cell lineage regulating oogenesis.

PLoS Biol 2020 04 27;18(4):e3000538. Epub 2020 Apr 27.

Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America.

Oogenesis is a complex developmental process that involves spatiotemporally regulated coordination between the germline and supporting, somatic cell populations. This process has been modeled extensively using the Drosophila ovary. Although different ovarian cell types have been identified through traditional means, the large-scale expression profiles underlying each cell type remain unknown. Using single-cell RNA sequencing technology, we have built a transcriptomic data set for the adult Drosophila ovary and connected tissues. Using this data set, we identified the transcriptional trajectory of the entire follicle-cell population over the course of their development from stem cells to the oogenesis-to-ovulation transition. We further identify expression patterns during essential developmental events that take place in somatic and germline cell types such as differentiation, cell-cycle switching, migration, symmetry breaking, nurse-cell engulfment, egg-shell formation, and corpus luteum signaling. Extensive experimental validation of unique expression patterns in both ovarian and nearby, nonovarian cells also led to the identification of many new cell type-and stage-specific markers. The inclusion of several nearby tissue types in this data set also led to our identification of functional convergence in expression between distantly related cell types such as the immune-related genes that were similarly expressed in immune cells (hemocytes) and ovarian somatic cells (stretched cells) during their brief phagocytic role in nurse-cell engulfment. Taken together, these findings provide new insight into the temporal regulation of genes in a cell-type specific manner during oogenesis and begin to reveal the relatedness in expression between cell and tissues types.
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http://dx.doi.org/10.1371/journal.pbio.3000538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205450PMC
April 2020

CRL4Mahj E3 ubiquitin ligase promotes neural stem cell reactivation.

PLoS Biol 2019 06 6;17(6):e3000276. Epub 2019 Jun 6.

Neuroscience and Behavioural Disorders Programme, Duke-NUS Medical School, Singapore, Singapore.

The ability of neural stem cells (NSCs) to transit between quiescence and proliferation is crucial for brain development and homeostasis. Drosophila Hippo pathway maintains NSC quiescence, but its regulation during brain development remains unknown. Here, we show that CRL4Mahj, an evolutionarily conserved E3 ubiquitin ligase, is essential for NSC reactivation (exit from quiescence). We demonstrate that damaged DNA-binding protein 1 (DDB1) and Cullin4, two core components of Cullin4-RING ligase (CRL4), are intrinsically required for NSC reactivation. We have identified a substrate receptor of CRL4, Mahjong (Mahj), which is necessary and sufficient for NSC reactivation. Moreover, we show that CRL4Mahj forms a protein complex with Warts (Wts/large tumor suppressor [Lats]), a kinase of the Hippo signaling pathway, and Mahj promotes the ubiquitination of Wts. Our genetic analyses further support the conclusion that CRL4Mahj triggers NSC reactivation by inhibition of Wts. Given that Cullin4B mutations cause mental retardation and cerebral malformation, similar regulatory mechanisms may be applied to the human brain.
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http://dx.doi.org/10.1371/journal.pbio.3000276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553684PMC
June 2019

Systematic analysis reveals tumor-enhancing and -suppressing microRNAs in epithelial tumors.

Oncotarget 2017 Dec 1;8(65):108825-108839. Epub 2017 Nov 1.

Department of Biological Science, Florida State University, Tallahassee, Florida, USA.

Despite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) (), combined with overexpression of an active form of oncogene ( ), and identified 51 mature miRNAs that changed significantly in tumorous discs. Followed by tumor enhancer and suppressor screens in sensitized genetic backgrounds, we identified 10 tumor-enhancing (TE) miRNAs and 11 tumor-suppressing (TS) miRNAs that contributed to the nTSG defect-induced tumorigenesis. Among these, four TE and three TS miRNAs have human homologs. From this study, we also identified 29 miRNAs that individually had no obvious role in enhancing or alleviating tumorigenesis despite their changed expression levels in nTSG tumors. This systematic analysis, which includes both RNA-Seq and functional studies, helps to categorize miRNAs into different groups based on their expression profile and functional relevance in epithelial tumorigenesis, whereas the evolutionarily conserved TE and TS miRNAs provide potential therapeutic targets for epithelial tumor treatment.
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http://dx.doi.org/10.18632/oncotarget.22226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752484PMC
December 2017

The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription.

EMBO J 2017 10 4;36(19):2887-2906. Epub 2017 Sep 4.

Aix Marseille Université, CNRS, IBDM, UMR 7288, Marseille, France

In metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that the Hox proteins AbdA and Ubx target gene promoters previously bound by the transcription pausing factor M1BP, containing paused Pol II and enriched with promoter-proximal Polycomb Group (PcG) proteins, yet lacking the classical H3K27me3 PcG signature. We found that AbdA binding to M1BP-regulated genes results in reduction in PcG binding, the release of paused Pol II, increases in promoter H3K4me3 histone marks and increased gene transcription. Linking transcription factors, PcG proteins and paused Pol II states, these data identify a two-step mechanism of Hox-driven transcription, with M1BP binding leading to Pol II recruitment followed by AbdA targeting, which results in a change in the chromatin landscape and enhanced transcription.
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http://dx.doi.org/10.15252/embj.201695751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623858PMC
October 2017

The SWI/SNF Complex Protein Snr1 Is a Tumor Suppressor in Imaginal Tissues.

Cancer Res 2017 02 6;77(4):862-873. Epub 2016 Dec 6.

Department of Biological Science, Florida State University, Tallahassee, Florida.

Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here, we use imaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades. Removal of Snr1 resulted in neoplastic tumorigenic overgrowth in imaginal epithelial tissues, whereas depletion of any other members of the SWI/SNF complex did not induce similar phenotypes. Unlike other components of the SWI/SNF complex that were detected only in the nucleus, Snr1 was observed in both the nucleus and the cytoplasm. Aberrant regulation of multiple signaling pathways, including Notch, JNK, and JAK/STAT, was responsible for tumor progression upon -depletion. Our results suggest that the cytoplasmic Snr1 may play a tumor suppressive role in imaginal tissues, offering a foundation for understanding the pivotal role of SMARCB1/hSNF5 in suppressing MRT during early childhood. .
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http://dx.doi.org/10.1158/0008-5472.CAN-16-0963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885033PMC
February 2017

Maternal AP determinants in the Drosophila oocyte and embryo.

Wiley Interdiscip Rev Dev Biol 2016 09 2;5(5):562-81. Epub 2016 Jun 2.

Department of Biological Science, Florida State University, Tallahassee, FL, USA.

An animal embryo cannot initiate its journey of forming a new life on its own. It must rely on maternally provided resources and inputs to kick-start its developmental process. In Drosophila, the initial polarities of the embryo along both the anterior-posterior (AP) and dorsal-ventral (DV) axes are also specified by maternal determinants. Over the past several decades, genetic and molecular studies have identified and characterized such determinants, as well as the zygotic genetic regulatory networks that control patterning in the early embryo. Extensive studies of oogenesis have also led to a detailed knowledge of the cellular and molecular interactions that control the formation of a mature egg. Despite these efforts, oogenesis and embryogenesis have been studied largely as separate problems, except for qualitative aspects with regard to maternal regulation of the asymmetric localization of maternal determinants. Can oogenesis and embryogenesis be viewed from a unified perspective at a quantitative level, and can that improve our understanding of how robust embryonic patterning is achieved? Here, we discuss the basic knowledge of the regulatory mechanisms controlling oogenesis and embryonic patterning along the AP axis. We explore properties of the maternal Bicoid gradient in relation to embryo size in search for a unified framework for robust AP patterning. WIREs Dev Biol 2016, 5:562-581. doi: 10.1002/wdev.235 For further resources related to this article, please visit the WIREs website.
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http://dx.doi.org/10.1002/wdev.235DOI Listing
September 2016

RNA helicase Belle/DDX3 regulates transgene expression in Drosophila.

Dev Biol 2016 Apr 18;412(1):57-70. Epub 2016 Feb 18.

Department of Biological Science, Florida State University, Tallahassee, FL, USA. Electronic address:

Belle (Bel), the Drosophila homolog of the yeast DEAD-box RNA helicase DED1 and human DDX3, has been shown to be required for oogenesis and female fertility. Here we report a novel role of Bel in regulating the expression of transgenes. Abrogation of Bel by mutations or RNAi induces silencing of a variety of P-element-derived transgenes. This silencing effect depends on downregulation of their RNA levels. Our genetic studies have revealed that the RNA helicase Spindle-E (Spn-E), a nuage RNA helicase that plays a crucial role in regulating RNA processing and PIWI-interacting RNA (piRNA) biogenesis in germline cells, is required for loss-of-bel-induced transgene silencing. Conversely, Bel abrogation alleviates the nuage-protein mislocalization phenotype in spn-E mutants, suggesting a competitive relationship between these two RNA helicases. Additionally, disruption of the chromatin remodeling factor Mod(mdg4) or the microRNA biogenesis enzyme Dicer-1 (Dcr-1) also alleviates the transgene-silencing phenotypes in bel mutants, suggesting the involvement of chromatin remodeling and microRNA biogenesis in loss-of-bel-induced transgene silencing. Finally we show that genetic inhibition of Bel function leads to de novo generation of piRNAs from the transgene region inserted in the genome, suggesting a potential piRNA-dependent mechanism that may mediate transgene silencing as Bel function is inhibited.
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http://dx.doi.org/10.1016/j.ydbio.2016.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814335PMC
April 2016

E(y)1/TAF9 mediates the transcriptional output of Notch signaling in Drosophila.

J Cell Sci 2014 Sep 11;127(Pt 17):3830-9. Epub 2014 Jul 11.

Department of Biological Science, Florida State University, Tallahassee, FL 32304-4295, USA

Transcriptional activation of Notch signaling targets requires the formation of a ternary complex that involves the intracellular domain of the Notch receptor (NICD), DNA-binding protein Suppressor of Hairless [Su(H), RPBJ in mammals] and coactivator Mastermind (Mam). Here, we report that E(y)1/TAF9, a component of the transcription factor TFIID complex, interacts specifically with the NICD-Su(H)-Mam complex to facilitate the transcriptional output of Notch signaling. We identified E(y)1/TAF9 in a large-scale in vivo RNA interference (RNAi) screen for genes that are involved in a Notch-dependent mitotic-to-endocycle transition in Drosophila follicle cells. Knockdown of e(y)1/TAF9 displayed Notch-mutant-like phenotypes and defects in target gene and activity reporter expression in both the follicle cells and wing imaginal discs. Epistatic analyses in these two tissues indicated that E(y)1/TAF9 functions downstream of Notch cleavage. Biochemical studies in S2 cells demonstrated that E(y)1/TAF9 physically interacts with the transcriptional effectors of Notch signaling Su(H) and NICD. Taken together, our data suggest that the association of the NICD-Su(H)-Mastermind complex with E(y)1/TAF9 in response to Notch activation recruits the transcription initiation complex to induce Notch target genes, coupling Notch signaling with the transcription machinery.
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http://dx.doi.org/10.1242/jcs.154583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150066PMC
September 2014

Uif, a large transmembrane protein with EGF-like repeats, can antagonize Notch signaling in Drosophila.

PLoS One 2012 30;7(4):e36362. Epub 2012 Apr 30.

State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Background: Notch signaling is a highly conserved pathway in multi-cellular organisms ranging from flies to humans. It controls a variety of developmental processes by stimulating the expression of its target genes in a highly specific manner both spatially and temporally. The diversity, specificity and sensitivity of the Notch signaling output are regulated at distinct levels, particularly at the level of ligand-receptor interactions.

Methodology/principal Findings: Here, we report that the Drosophila gene uninflatable (uif), which encodes a large transmembrane protein with eighteen EGF-like repeats in its extracellular domain, can antagonize the canonical Notch signaling pathway. Overexpression of Uif or ectopic expression of a neomorphic form of Uif, Uif*, causes Notch signaling defects in both the wing and the sensory organ precursors. Further experiments suggest that ectopic expression of Uif* inhibits Notch signaling in cis and acts at a step that is dependent on the extracellular domain of Notch. Our results suggest that Uif can alter the accessibility of the Notch extracellular domain to its ligands during Notch activation.

Conclusions/significance: Our study shows that Uif can modulate Notch activity, illustrating the importance of a delicate regulation of this signaling pathway for normal patterning.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036362PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340373PMC
September 2012

CAF-1 is essential for Drosophila development and involved in the maintenance of epigenetic memory.

Dev Biol 2007 Nov 29;311(1):213-22. Epub 2007 Aug 29.

National Laboratory of Biomacromolecules and State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, The Chinese Academy of Sciences, Datun Road 15, Chaoyang District, Beijing 100101, China.

DNA synthesis during S-phase and upon DNA repair is accompanied by chromatin assembly. The chromatin assembly factor CAF-1 has been biochemically well-characterized to deposit histones onto newly synthesized DNA. To gain insights into the in vivo functions of CAF-1 in Drosophila, we generated null mutants of the largest subunit of dCAF-1, dCAF-1-p180. We show that, unlike CAF-1 mutant yeast, dCAF-1-p180 mutant flies are hemizygous lethal. Removal of maternal dCAF-1-p180 activity by germline clones blocks oogenesis. Tissue-specific deletion of dCAF-1-p180 in the eye primordia disrupts eye development. In addition, reduction of dCAF-1-p180 activity suppresses gene silencing at heterochromatin and antagonizes Polycomb-mediated cell fate determination. Furthermore, heterozygous dCAF-1-p180 mutant flies display an increased sensitivity to gamma-irradiation and a reduced efficiency in recombinational double strand break (DSB) repair. Our experiments also show that human hCAF-1-p150 can rescue the dCAF-1-p180 mutant flies, demonstrating a functional conservation of eukaryotic CAF-1 activities in vivo. Together, our results establish that dCAF-1-p180 is an essential gene for Drosophila development and further underscore the importance of dCAF-1 in regulating gene expression and DNA repair in vivo.
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http://dx.doi.org/10.1016/j.ydbio.2007.08.039DOI Listing
November 2007

Glucose-6-phosphate dehydrogenase plays a pivotal role in nitric oxide-involved defense against oxidative stress under salt stress in red kidney bean roots.

Plant Cell Physiol 2007 Mar 8;48(3):511-22. Epub 2007 Feb 8.

Key Laboratory of Arid and Grassland Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, PR China.

The pivotal role of glucose-6-phosphate dehydrogenase (G-6-PDH)-mediated nitric oxide (NO) production in the tolerance to oxidative stress induced by 100 mM NaCl in red kidney bean (Phaseolus vulgaris) roots was investigated. The results show that the G-6-PDH activity was enhanced rapidly in the presence of NaCl and reached a maximum at 100 mM. Western blot analysis indicated that the increase of G-6-PDH activity in the red kidney bean roots under 100 mM NaCl was mainly due to the increased content of the G-6-PDH protein. NO production and nitrate reductase (NR) activity were also induced by 100 mM NaCl. The NO production was reduced by NaN(3) (an NR inhibitor), but not affected by N(omega)-nitro-L-arginine (L-NNA) (an NOS inhibitor). Application of 2.5 mM Na(3)PO(4), an inhibitor of G-6-PDH, blocked the increase of G-6-PDH and NR activity, as well as NO production in red kidney bean roots under 100 mM NaCl. The activities of antioxidant enzymes in red kidney bean roots increased in the presence of 100 mM NaCl or sodium nitroprusside (SNP), an NO donor. The increased activities of all antioxidant enzymes tested at 100 mM NaCl were completely inhibited by 2.5 mM Na(3)PO(4). Based on these results, we conclude that G-6-PDH plays a pivotal role in NR-dependent NO production, and in establishing tolerance of red kidney bean roots to salt stress.
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http://dx.doi.org/10.1093/pcp/pcm020DOI Listing
March 2007
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