scholarly journals Transcriptional profiling reveals the transcription factor networks regulating the survival of striatal neurons

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lin Yang ◽  
Zihao Su ◽  
Ziwu Wang ◽  
Zhenmeiyu Li ◽  
Zicong Shang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Profiling ◽  
Conditional Knockout ◽  
Biological Processes ◽  
Rna Seq ◽  
Striatal Neurons ◽  
Transcriptome Profile ◽  
Functional Changes ◽  
Transcription Factor Networks ◽  
Normal Embryonic Development

AbstractThe striatum is structurally highly diverse, and its organ functionality critically depends on normal embryonic development. Although several studies have been conducted on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive transcriptome profile that allows us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington’s disease (HD). Furthermore, we applied an integrative transcriptomic profiling approach based on machine learning to systematically map a global landscape of 277 transcription factor (TF) networks. Most of these TF networks are linked to biological processes, and some unannotated genes provide information about the corresponding mechanisms. For example, we found that the Meis2 and Six3 were crucial for the survival of striatal neurons, which were verified using conditional knockout (CKO) mice. Finally, we used RNA-Seq to speculate their downstream targets.

scholarly journals Transcriptional Profiling Reveals the Transcription Factor Networks Regulating the Survival of Striatal Neurons

2020 ◽  
Author(s):  
Lin Yang ◽  
Zihao Su ◽  
Xiaolei Song ◽  
Zhenmeiyu Li ◽  
Ziwu Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neuronal Apoptosis ◽  
Developmental Stages ◽  
Transcriptional Profiling ◽  
Conditional Knockout ◽  
Gene Products ◽  
Rna Seq ◽  
Striatal Neurons ◽  
Functional Changes ◽  
Transcription Factor Networks

AbstractThe striatum is structurally highly diverse and its organ functionality critically depends on a normal embryonic development. Although several studies on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive temporal transcriptome atlas of the mouse striatum at multiple developmental stages. Quantitative analysis of 15443 gene products allows us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington’s disease (HD). More importantly, we provided the global landscape of 277 transcription factor (TF) networks based on co-expression analysis and machine learning. Furthermore, we identified the hub TFs Six3 and Meis2 which are involved in regulating the apoptosis of striatal neurons. Finally, using conditional knockout (CKO) mice and RNA-Seq data, we verified that Six3 and Meis2 indeed regulated neuronal apoptosis and inferred their downstream targets in the striatum.

scholarly journals Molecular regulation of Snai2 in development and disease

2019 ◽  
Vol 132 (23) ◽  
Author(s):  
Wenhui Zhou ◽  
Kayla M. Gross ◽  
Charlotte Kuperwasser
Keyword(s):  
Transcription Factor ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Zinc Finger Protein ◽  
Main Role ◽  
Biological Processes ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Damage Repair

ABSTRACT The transcription factor Snai2, encoded by the SNAI2 gene, is an evolutionarily conserved C2H2 zinc finger protein that orchestrates biological processes critical to tissue development and tumorigenesis. Initially characterized as a prototypical epithelial-to-mesenchymal transition (EMT) transcription factor, Snai2 has been shown more recently to participate in a wider variety of biological processes, including tumor metastasis, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair. The main role of Snai2 in controlling such processes involves facilitating the epigenetic regulation of transcriptional programs, and, as such, its dysregulation manifests in developmental defects, disruption of tissue homeostasis, and other disease conditions. Here, we discuss our current understanding of the molecular mechanisms regulating Snai2 expression, abundance and activity. In addition, we outline how these mechanisms contribute to disease phenotypes or how they may impact rational therapeutic targeting of Snai2 dysregulation in human disease.

scholarly journals Transcriptome profiling of developing leaf and shoot apices to reveal the molecular mechanism and co-expression genes responsible for the wheat heading date

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuxin Yang ◽  
Xueying Zhang ◽  
Lifen Wu ◽  
Lichao Zhang ◽  
Guoxiang Liu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Flowering Time ◽  
Heading Date ◽  
Yield Component ◽  
Potential Candidate ◽  
Rna Seq ◽  
Nucleotide Synthesis ◽  
Light Reaction ◽  
Grain Number Per Spike ◽  
Double Ridge

Abstract Background Wheat is one of the most widely planted crops worldwide. The heading date is important for wheat environmental adaptability, as it not only controls flowering time but also determines the yield component in terms of grain number per spike. Results In this research, homozygous genotypes with early and late heading dates derived from backcrossed progeny were selected to conduct RNA-Seq analysis at the double ridge stage (W2.0) and androgynous primordium differentiation stage (W3.5) of the leaf and apical meristem, respectively. In total, 18,352 differentially expressed genes (DEGs) were identified, many of which are strongly associated with wheat heading date genes. Gene Ontology (GO) enrichment analysis revealed that carbohydrate metabolism, trehalose metabolic process, photosynthesis, and light reaction are closely related to the flowering time regulation pathway. Based on MapMan metabolic analysis, the DEGs are mainly involved in the light reaction, hormone signaling, lipid metabolism, secondary metabolism, and nucleotide synthesis. In addition, 1,225 DEGs were annotated to 45 transcription factor gene families, including LFY, SBP, and MADS-box transcription factors closely related to flowering time. Weighted gene co-expression network analysis (WGCNA) showed that 16, 336, 446, and 124 DEGs have biological connections with Vrn1-5 A, Vrn3-7B, Ppd-1D, and WSOC1, respectively. Furthermore, TraesCS2D02G181400 encodes a MADS-MIKC transcription factor and is co-expressed with Vrn1-5 A, which indicates that this gene may be related to flowering time. Conclusions RNA-Seq analysis provided transcriptome data for the wheat heading date at key flower development stages of double ridge (W2.0) and androgynous primordium differentiation (W3.5). Based on the DEGs identified, co-expression networks of key flowering time genes in Vrn1-5 A, Vrn3-7B, WSOC1, and Ppd-1D were established. Moreover, we discovered a potential candidate flowering time gene, TraesCS2D02G181400. Taken together, these results serve as a foundation for further study on the regulatory mechanism of the wheat heading date.

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.

scholarly journals Identification of Potential Key lncRNAs in the Context of Mouse Myeloid Differentiation by Systematic Transcriptomics Analysis

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 630
Author(s):  
Yongqing Lan ◽  
Meng Li ◽  
Shuangli Mi
Keyword(s):  
Transcription Factor ◽  
Cell Model ◽  
Myeloid Differentiation ◽  
Rna Seq ◽  
Hematopoietic Differentiation ◽  
Granulocytic Differentiation ◽  
Expression Of Genes ◽  
Non Coding Rnas

Hematopoietic differentiation is a well-orchestrated process by many regulators such as transcription factor and long non-coding RNAs (lncRNAs). However, due to the large number of lncRNAs and the difficulty in determining their roles, the study of lncRNAs is a considerable challenge in hematopoietic differentiation. Here, through gene co-expression network analysis over RNA-seq data generated from representative types of mouse myeloid cells, we obtained a catalog of potential key lncRNAs in the context of mouse myeloid differentiation. Then, employing a widely used in vitro cell model, we screened a novel lncRNA, named Gdal1 (Granulocytic differentiation associated lncRNA 1), from this list and demonstrated that Gdal1 was required for granulocytic differentiation. Furthermore, knockdown of Cebpe, a principal transcription factor of granulocytic differentiation regulation, led to down-regulation of Gdal1, but not vice versa. In addition, expression of genes involved in myeloid differentiation and its regulation, such as Cebpa, were influenced in Gdal1 knockdown cells with differentiation blockage. We thus systematically identified myeloid differentiation associated lncRNAs and substantiated the identification by investigation of one of these lncRNAs on cellular phenotype and gene regulation levels. This study promotes our understanding of the regulation of myeloid differentiation and the characterization of roles of lncRNAs in hematopoietic system.

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