scholarly journals Chromatin run-on reveals the transcriptional etiology of glioblastoma multiforme

2017 ◽  
Author(s):  
Tinyi Chu ◽  
Edward J. Rice ◽  
Gregory T. Booth ◽  
H. Hans Salamanca ◽  
Zhong Wang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Open Chromatin ◽  
Rna Seq ◽  
Malignant Tissue ◽  
Expression Of Genes ◽  
Genomic Tools ◽  
Input Sample ◽  
Normal Human ◽  
Molecular Etiology ◽  
Developing Nervous System

AbstractThe human genome encodes a variety of poorly understood RNA species that remain challenging to identify using existing genomic tools. We developed chromatin run-on and sequencing (ChRO-seq) to map the location of RNA polymerase using virtually any input sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in primary human glioblastoma (GBM) brain tumors. Whereas enhancers discovered in primary GBMs resemble open chromatin in the normal human brain, rare enhancers activated in malignant tissue drive regulatory programs similar to the developing nervous system. We identified enhancers that regulate genes characteristic of each known GBM subtype, identified transcription factors that drive them, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.

scholarly journals Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Lago ◽  
Matteo Nadai ◽  
Filippo M. Cernilogar ◽  
Maryam Kazerani ◽  
Helena Domíniguez Moreno ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Gene ◽  
Open Chromatin ◽  
Rna Seq ◽  
Transcript Levels ◽  
Promoter Sequences ◽  
G Quadruplex ◽  
Cell Type Specific ◽  
Folding State

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity. By G4-ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus, G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s to strongly emerge as new epigenetic regulators of the transcription machinery.

scholarly journals Differential Expression of Genes Related to the Formation of Giant Leaves in Triploid Poplar

Forests ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 920 ◽  
Author(s):  
Kang Du ◽  
Qiang Han ◽  
Ying Zhang ◽  
Xiangyang Kang
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Leaf Growth ◽  
Growth Hormones ◽  
Endogenous Hormones ◽  
Rna Seq ◽  
Hormone Metabolism ◽  
Expression Of Genes ◽  
Genes Expression ◽  
Differential Expression Of Genes

Plant polyploids tend to have large leaves, but their formation mechanism has not yet been well explained. Therefore, daily transcriptomic differences between triploids and diploids from a synthetic Populus sect. Tacamahaca three times a day (i.e., 04:00, 09:00, and 21:00) were investigated using high-throughput RNA-seq analysis. In this study, we identified several transcription factors associated with giant leaves. The combined effects included the high expression of several transcription factors (WRKY, MYB, etc.) and hormone-related genes (e.g., activates auxin, cytokine, and brassinosteroid synthesis-related genes) that accelerate the synthesis and accumulation of endogenous hormones. High levels of growth hormones were maintained by reducing the genes’ expression of hormone metabolism and degradation. The coordination of hormones accumulated sufficient materials and energy for leaf growth and development. Thereby, cell division and growth were accelerated which enhanced the photosynthesis of leaves, and the increased accumulation of photosynthetic products led to giant triploid leaves. This study lays the foundation for revealing the molecular mechanisms in the formation of giant leaves in polyploids.

scholarly journals Promoter G-quadruplexes and transcription factors cooperate to shape the cell type-specific transcriptome

2020 ◽  
Author(s):  
Sara Lago ◽  
Filippo M. Cernilogar ◽  
Maryam Kazerani ◽  
Helena Domíniguez Moreno ◽  
Matteo Nadai ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Specific Gene ◽  
Open Chromatin ◽  
Rna Seq ◽  
Transcript Levels ◽  
Promoter Sequences ◽  
G Quadruplex ◽  
Cell Type Specific ◽  
Folding State

AbstractCell identity is maintained by activation of cell-specific gene programs, regulated by epigenetic marks, transcription factors and chromatin organization1-3. DNA G-quadruplex (G4)-folded regions in cells were reported to be associated with either increased or decreased transcriptional activity4,5. By G4 ChIP-seq/RNA-seq analysis on liposarcoma cells we confirmed that G4s in promoters are invariably associated with high transcription levels in open chromatin. Comparing G4 presence, location and transcript levels in liposarcoma cells to available data on keratinocytes, we showed that the same promoter sequences of the same genes in the two cell lines had different G4-folding state: high transcript levels consistently associated with high G4-folding. Transcription factors AP-1 and SP1, whose binding sites were the most significantly represented in G4-folded sequences, coimmunoprecipitated with their G4-folded promoters. Thus G4s and their associated transcription factors cooperate to determine cell-specific transcriptional programs, making G4s strongly emerge as new epigenetic regulators of the transcription machinery.

The Role of Retinoblastoma Protein in Cell Cycle Regulation: An Updated Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Rabih Roufayel ◽  
Rabih Mezher ◽  
Kenneth B. Storey
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Cycle Control ◽  
Expression Of Genes ◽  
E2f Transcription Factor ◽  
Cellular Energetics ◽  
Development And Differentiation ◽  
E2f Transcription Factors ◽  
Rb Phosphorylation

: Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provide a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.

scholarly journals NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells

2021 ◽  
Vol 22 (11) ◽  
pp. 5902
Author(s):  
Stefan Nagel ◽  
Claudia Pommerenke ◽  
Corinna Meyer ◽  
Hans G. Drexler
Keyword(s):  
Dendritic Cells ◽  
Transcription Factors ◽  
Cell Lines ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Homeobox Gene ◽  
Leukemia Cell Line ◽  
Specific Gene ◽  
Rna Seq ◽  
And Function

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

scholarly journals RNA-Seq Provides New Insights into the Molecular Events Involved in “Ball-Skin versus Bladder Effect” on Fruit Cracking in Litchi

2021 ◽  
Vol 22 (1) ◽  
pp. 454
Author(s):  
Jun Wang ◽  
Xiao Fang Wu ◽  
Yong Tang ◽  
Jian Guo Li ◽  
Ming Lei Zhao
Keyword(s):  
Transcription Factors ◽  
Plant Hormones ◽  
Fruit Development ◽  
Economic Value ◽  
Lipid Synthesis ◽  
Expression Level ◽  
Agricultural Product ◽  
Rna Seq ◽  
Fruit Cracking ◽  
Molecular Events

Fruit cracking is a disorder of fruit development in response to internal or external cues, which causes a loss in the economic value of fruit. Therefore, exploring the mechanism underlying fruit cracking is of great significance to increase the economic yield of fruit trees. However, the molecular mechanism underlying fruit cracking is still poorly understood. Litchi, as an important tropical and subtropical fruit crop, contributes significantly to the gross agricultural product in Southeast Asia. One important agricultural concern in the litchi industry is that some famous varieties with high economic value such as ‘Nuomici’ are susceptible to fruit cracking. Here, the cracking-susceptible cultivar ‘Nuomici’ and cracking-resistant cultivar ‘Huaizhi’ were selected, and the samples including pericarp and aril during fruit development and cracking were collected for RNA-Seq analysis. Based on weighted gene co-expression network analysis (WGCNA) and the “ball-skin versus bladder effect” theory (fruit cracking occurs upon the aril expanding pressure exceeds the pericarp strength), it was found that seven co-expression modules genes (1733 candidate genes) were closely associated with fruit cracking in ‘Nuomici’. Importantly, we propose that the low expression level of genes related to plant hormones (Auxin, Gibberellins, Ethylene), transcription factors, calcium transport and signaling, and lipid synthesis might decrease the mechanical strength of pericarp in ‘Nuomici’, while high expression level of genes associated with plant hormones (Auxin and abscisic acid), transcription factors, starch/sucrose metabolism, and sugar/water transport might increase the aril expanding pressure, thereby resulting in fruit cracking in ‘Nuomici’. In conclusion, our results provide comprehensive molecular events involved in the “ball-skin versus bladder effect” on fruit cracking in litchi.

scholarly journals Identification of New Transcription Factors that Can Promote Pluripotent Reprogramming

2021 ◽  
Author(s):  
Ping Huang ◽  
Jieying Zhu ◽  
Yu Liu ◽  
Guihuan Liu ◽  
Ran Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Rna Sequencing ◽  
Human Urine ◽  
Embryonic Stem ◽  
Rna Seq ◽  
Reprogramming Efficiency ◽  
Yamanaka Factors ◽  
Urine Cells

Abstract Background Four transcription factors, Oct4, Sox2, Klf4, and c-Myc (the Yamanka factors), can reprogram somatic cells to induced pluripotent stem cells (iPSCs). Many studies have provided a number of alternative combinations to the non-Yamanaka factors. However, it is clear that many additional transcription factors that can generate iPSCs remain to be discovered. Methods The chromatin accessibility and transcriptional level of human embryonic stem cells and human urine cells were compared by Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) to identify potential reprogramming factors. Selected transcription factors were employed to reprogram urine cells, and the reprogramming efficiency was measured. Urine-derived iPSCs were detected for pluripotency by Immunofluorescence, quantitative polymerase chain reaction, RNA sequencing and teratoma formation test. Finally, we assessed the differentiation potential of the new iPSCs to cardiomyocytes in vitro. Results ATAC-seq and RNA-seq datasets predicted TEAD2, TEAD4 and ZIC3 as potential factors involved in urine cell reprogramming. Transfection of TEAD2, TEAD4 and ZIC3 (in the presence of Yamanaka factors) significantly improved the reprogramming efficiency of urine cells. We confirmed that the newly generated iPSCs possessed pluripotency characteristics similar to normal H1 embryonic stem cells. We also confirmed that the new iPSCs could differentiate to functional cardiomyocytes. Conclusions In conclusion, TEAD2, TEAD4 and ZIC3 can increase the efficiency of reprogramming human urine cells into iPSCs, and provides a new stem cell sources for the clinical application and modeling of cardiovascular disease. Graphical abstract

scholarly journals A Synergistic Anti-Diabetic Effect by Ginsenosides Rb1 and Rg3 through Adipogenic and Insulin Signaling Pathways in 3T3-L1 Cells

2021 ◽  
Vol 11 (4) ◽  
pp. 1725
Author(s):  
Hee-Do Hong ◽  
Sun-Il Choi ◽  
Ok-Hwan Lee ◽  
Young-Cheul Kim
Keyword(s):  
Transcription Factors ◽  
Insulin Signaling ◽  
Adipocyte Differentiation ◽  
Red Ginseng ◽  
Inhibitory Effects ◽  
Rt Pcr ◽  
High Concentration ◽  
Expression Of Genes ◽  
The Individual ◽  
Maximal Expression

Although ginsenosides Rb1 and Rg3 have been identified as the significant ginsenosides found in red ginseng that confer anti-diabetic actions, it is unclear whether insulin-sensitizing effects are mediated by the individual compounds or by their combination. To determine the effect of ginsenosides Rb1 and Rg3 on adipocyte differentiation, 3T3-L1 preadipocytes were induced to differentiate the standard hormonal inducers in the absence or presence of ginsenosides Rb1 or Rg3. Additionally, we determined the effects of Rb1, Rg3, or their combination on the expression of genes related to adipocyte differentiation, adipogenic transcription factors, and the insulin signaling pathway in 3T3-L1 cells using semi-quantitative RT-PCR. Rb1 significantly increased the expression of CEBPα, PPARγ, and aP2 mRNAs. However, Rg3 exerted its maximal stimulatory effect on these genes at 1 μM concentration, while a high concentration (50 μM) showed inhibitory effects. Similarly, treatment with Rb1 and Rg3 (1 μM) increased the expression of IRS-1, Akt, PI3K, GLUT4, and adiponectin. Importantly, co-treatment of Rb1 and Rg3 (9:1) induced the maximal expression levels of these mRNAs. Our data indicate that the anti-diabetic activity of red ginseng is, in part, mediated by synergistic actions of Rb1 and Rg3, further supporting the significance of minor Rg3.

scholarly journals HbxB Is a Key Regulator for Stress Response and β-Glucan Biogenesis in Aspergillus nidulans

2021 ◽  
Vol 9 (1) ◽  
pp. 144
Author(s):  
Sung-Hun Son ◽  
Mi-Kyung Lee ◽  
Ye-Eun Son ◽  
Hee-Soo Park
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Aspergillus Nidulans ◽  
Deletion Mutant ◽  
Phenotypic Analysis ◽  
Spore Viability ◽  
Fungal Development ◽  
Expression Of Genes ◽  
Trehalose Biosynthesis

Homeobox transcription factors are conserved in eukaryotes and act as multi-functional transcription factors in filamentous fungi. Previously, it was demonstrated that HbxB governs fungal development and spore viability in Aspergillus nidulans. Here, the role of HbxB in A. nidulans was further characterized. RNA-sequencing revealed that HbxB affects the transcriptomic levels of genes associated with trehalose biosynthesis and response to thermal, oxidative, and radiation stresses in asexual spores called conidia. A phenotypic analysis found that hbxB deletion mutant conidia were more sensitive to ultraviolet stress. The loss of hbxB increased the mRNA expression of genes associated with β-glucan degradation and decreased the amount of β-glucan in conidia. In addition, hbxB deletion affected the expression of the sterigmatocystin gene cluster and the amount of sterigmatocystin. Overall, these results indicated that HbxB is a key transcription factor regulating trehalose biosynthesis, stress tolerance, β-glucan degradation, and sterigmatocystin production in A.nidulans conidia.

scholarly journals EPEN-30. C11ORF95-RELA FUSION PROTEIN ENGAGES NOVEL GENOMIC LOCI TO DRIVE MURINE EPENDYMOMA GROWTH

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii314-iii314
Author(s):  
Amir Arabzade ◽  
Yanhua Zhao ◽  
Srinidhi Varadharajan ◽  
Hsiao-Chi Chen ◽  
Austin Stuckert ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Binding Sites ◽  
Molecular Targets ◽  
Lead Target ◽  
Open Chromatin ◽  
Rna Seq ◽  
In Utero Electroporation ◽  
Pathway Activation ◽  
Mouse Cells ◽  
Shed Light

Abstract RATIONALE Over 70% of supratentorial (ST) ependymoma are characterized by an oncogenic fusion between C11ORF95 and RELA. C11ORF95-RELA fusion is frequently the sole genetic driver detected in ST ependymoma, thus ranking this genomic event as a lead target for therapeutic investigation. RELA is a transcription factor (TF) central to mediating NF-kB pathway activation in processes such as inflammation, cellular metabolism, and chemotaxis. HYPOTHESIS: We posited that C11ORF95-RELA acts as an oncogenic TF that aberrantly shapes the tumor epigenome to drive aberrant transcription. Approach: To this end we developed an in utero electroporation (IUE) mouse model of ependymoma to express C11ORF95-RELA during embryonic development. Our IUE approach allowed us to develop C11ORF95-RELA driven tumor models and cell lines. We comprehensively characterized the epigenome and transcriptome of C11ORF95-RELA fusion driven mouse cells by H3K27ac ChIP-seq, ATAC-seq, and RNA-seq. RESULTS This data revealed that: 1) C11ORF95-RELA directly engages ‘open’ chromatin and is enriched at regions with known RELA TF binding sites as well as novel genomic loci/motifs, 2) C11ORF95-RELA preferentially binds to both H3K27ac (active) enhancers and promoters, and 3) Bound C11ORF95-RELA promoter loci are associated with increased transcription of genes shared with human ependymoma. CONCLUSION Our findings shed light on the transcriptional mechanisms of C11ORF95-RELA, and reveal downstream targets that may represent cancer dependency genes and molecular targets.

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