A genome-wide transcriptome profiling reveals the early molecular events during callus initiation in Arabidopsis multiple organs

AbstractCerebral amyloid angiopathy (CAA) contributes to accelerated cognitive decline in Alzheimer’s disease (AD) dementia and is a common finding at autopsy. The APOEε4 allele and male sex have previously been reported to associate with increased CAA in AD. To inform biomarker and therapeutic target discovery, we aimed to identify additional genetic risk factors and biological pathways involved in this vascular component of AD etiology. We present a genome-wide association study of CAA pathology in AD cases and report sex- and APOE-stratified assessment of this phenotype. Genome-wide genotypes were collected from 853 neuropathology-confirmed AD cases scored for CAA across five brain regions, and imputed to the Haplotype Reference Consortium panel. Key variables and genome-wide genotypes were tested for association with CAA in all individuals and in sex and APOEε4 stratified subsets. Pathway enrichment was run for each of the genetic analyses. Implicated loci were further investigated for functional consequences using brain transcriptome data from 1,186 samples representing seven brain regions profiled as part of the AMP-AD consortium. We confirmed association of male sex, AD neuropathology and APOEε4 with increased CAA, and identified a novel locus, LINC-PINT, associated with lower CAA amongst APOEε4-negative individuals (rs10234094-C, beta = −3.70 [95% CI −0.49—−0.24]; p = 1.63E-08). Transcriptome profiling revealed higher LINC-PINT expression levels in AD cases, and association of rs10234094-C with altered LINC-PINT splicing. Pathway analysis indicates variation in genes involved in neuronal health and function are linked to CAA in AD patients. Further studies in additional and diverse cohorts are needed to assess broader translation of our findings.

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Comparative Transcriptome Profiling of High and Low oil yielding Santalum album L.

10.1101/2021.05.12.443750 ◽

2021 ◽

Author(s):

Tanzeem Fatima ◽

Rangachari Krishnan ◽

Ashutosh Srivastava ◽

Vageeshbabu S. Hanur ◽

M. Srinivasa Rao

Keyword(s):

Transcriptome Profiling ◽

Santalum Album ◽

Rna Seq ◽

Improvement Program ◽

East Indian ◽

Kegg Pathways ◽

Oil Biosynthesis ◽

Genome Wide ◽

A Genome ◽

Santalum Album L

East Indian Sandalwood (Santalum album L.) is highly valued for its heartwood and its oil. There have been no efforts to comparative study of high and low oil yielding genetically identical sandalwood trees grown in similar climatic condition. Thus we intend to study a genome wide transcriptome analysis to identify the corresponding genes involved in high oil biosynthesis in S. album. In this study, 15 years old S. album (SaSHc and SaSLc) genotypes were targeted for analysis to understand the contribution of genetic background on high oil biosynthesis in S. album. A total of 28,959187 and 25,598869 raw PE reads were generated by the Illumina sequencing. 2.12 million and 1.811 million coding sequences were obtained in respective accessions. Based on the GO terms, functional classification of the CDS 21262, & 18113 were assigned into 26 functional groups of three GO categories; (4,168; 3,641) for biological process (5,758;4,971) cellular component and (5,108;4,441) for molecular functions. Total 41,900 and 36,571 genes were functionally annotated and KEGG pathways of the DEGs resulted 213 metabolic pathways. In this, 14 pathways were involved in secondary metabolites biosynthesis pathway in S. album. Among 237 cytochrome families, nine groups of cytochromes were participated in high oil biosynthesis. 16,665 differentially expressed genes were commonly detected in both the accessions (SaHc and SaSLc). The results showed that 784 genes were upregulated and 339 genes were downregulated in SaHc whilst 635 upregulated 299 downregulated in SaSLc S. album. RNA-Seq results were further validated by quantitative RT-PCR. Maximum Blast hits were found to be against Vitis vinifera. From this study we have identified additional number of cytochrome family in SaHc. The accessibility of a RNA-Seq for high oil yielding sandalwood accessions will have broader associations for the conservation and selection of superior elite samples/populations for further genetic improvement program.

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Generation and Transcriptome Profiling of Slr1-d7 and Slr1-d8 Mutant Lines with a New Semi-Dominant Dwarf Allele of SLR1 Using the CRISPR/Cas9 System in Rice

International Journal of Molecular Sciences ◽

10.3390/ijms21155492 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5492 ◽

Cited By ~ 1

Author(s):

Yu Jin Jung ◽

Jong Hee Kim ◽

Hyo Ju Lee ◽

Dong Hyun Kim ◽

Jihyeon Yu ◽

...

Keyword(s):

Gene Expression Analysis ◽

Transcriptome Profiling ◽

Rna Seq ◽

Loss Of Function ◽

Amino Acid Motif ◽

Dwarf Phenotype ◽

Genome Wide ◽

A Genome ◽

Mutant Lines ◽

Genome Wide Gene Expression

The rice SLR1 gene encodes the DELLA protein (protein with DELLA amino acid motif), and a loss-of-function mutation is dwarfed by inhibiting plant growth. We generate slr1-d mutants with a semi-dominant dwarf phenotype to target mutations of the DELLA/TVHYNP domain using CRISPR/Cas9 genome editing in rice. Sixteen genetic edited lines out of 31 transgenic plants were generated. Deep sequencing results showed that the mutants had six different mutation types at the target site of the TVHYNP domain of the SLR1 gene. The homo-edited plants selected individuals without DNA (T-DNA) transcribed by segregation in the T1 generation. The slr1-d7 and slr1-d8 plants caused a gibberellin (GA)-insensitive dwarf phenotype with shrunken leaves and shortened internodes. A genome-wide gene expression analysis by RNA-seq indicated that the expression levels of two GA-related genes, GA20OX2 (Gibberellin oxidase) and GA3OX2, were increased in the edited mutant plants, suggesting that GA20OX2 acts as a convert of GA12 signaling. These mutant plants are required by altering GA responses, at least partially by a defect in the phytohormone signaling system process and prevented cell elongation. The new mutants, namely, the slr1-d7 and slr1-d8 lines, are valuable semi-dominant dwarf alleles with potential application value for molecule breeding using the CRISPR/Cas9 system in rice.

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An optimized ChIP-Seq framework for profiling of histone modifications in Chromochloris zofingiensis

10.1101/2021.11.11.468265 ◽

2021 ◽

Author(s):

Daniela Strenkert ◽

Matthew Mingay ◽

Stefan Schmollinger ◽

Cindy Chen ◽

Ronan C O'Malley ◽

...

Keyword(s):

Fragment Size ◽

Transcriptome Profiling ◽

Formaldehyde Concentration ◽

Structural Annotation ◽

Transcription Start Sites ◽

Genome Wide ◽

Chip Experiment ◽

A Genome ◽

Dna Shearing ◽

Chromochloris Zofingiensis

The eukaryotic green alga Chromochloris zofingiensis is a reference organism for studying carbon partitioning and a promising candidate for the production of biofuel precursors. Recent transcriptome profiling transformed our understanding of its biology and generally algal biology, but epigenetic regulation remains understudied and represents a fundamental gap in our understanding of algal gene expression. Chromatin Immunoprecipitation followed by deep sequencing (ChIP-Seq) is a powerful tool for the discovery of such mechanisms, by identifying genome-wide histone modification patterns and transcription factor-binding sites alike. Here, we established a ChIP-Seq framework for Chr. zofingiensis yielding over 20 million high quality reads per sample. The most critical steps in a ChIP experiment were optimized, including DNA shearing to obtain an average DNA fragment size of 250 bp and assessment of the recommended formaldehyde concentration for optimal DNA-protein crosslinking. We used this ChIP-Seq framework to generate a genome-wide map of the H3K4me3 distribution pattern and to integrate these data with matching RNA-Seq data. In line with observations from other organisms, H3K4me3 marks predominantly transcription start sites of genes. Our H3K4me3 ChIP-Seq data will pave the way for improved genome structural annotation in the emerging reference alga Chr. zofingiensis.

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KLF4 binding is involved in the organization and regulation of 3D enhancer networks during acquisition and maintenance of pluripotency

10.1101/382473 ◽

2018 ◽

Cited By ~ 1

Author(s):

Dafne Campigli Di Giammartino ◽

Andreas Kloetgen ◽

Alexander Polyzos ◽

Yiyuan Liu ◽

Daleum Kim ◽

...

Keyword(s):

Cell Fate ◽

Binding Sites ◽

Target Gene ◽

Embryonic Fibroblasts ◽

Molecular Events ◽

Genome Wide ◽

A Genome ◽

Integrative View ◽

Transcriptional Changes ◽

Complex Activities

SUMMARYCell fate transitions are accompanied by global transcriptional, epigenetic and topological changes driven by transcription factors (TFs), as is strikingly exemplified by reprogramming somatic cells to pluripotent stem cells (PSCs) via expression of OCT4, KLF4, SOX2 and cMYC. How TFs orchestrate the complex molecular changes around their target gene loci in a temporal manner remains incompletely understood. Here, using KLF4 as a paradigm, we provide the first TF-centric view of chromatin reorganization and its association to 3D enhancer rewiring and transcriptional changes of linked genes during reprogramming of mouse embryonic fibroblasts (MEFs) to PSCs. Inducible depletion of KLF factors in PSCs caused a genome-wide decrease in the connectivity of enhancers, while disruption of individual KLF4 binding sites from PSC-specific enhancers was sufficient to impair enhancer-promoter contacts and reduce expression of associated genes. Our study provides an integrative view of the complex activities of a lineage-specifying TF during a controlled cell fate transition and offers novel insights into the order and nature of molecular events that follow TF binding.

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Expression of MSX1, HOXA11 and TP53I3 in the endometrium associated with the onset of pregnancy after repeated failed IVF attempts in patients with tubo-peritoneal factor infertility

GYNECOLOGY ◽

10.26442/20795696.2020.1.200028 ◽

2020 ◽

Vol 22 (1) ◽

pp. 23-28

Author(s):

Ekaterina A. Knyazeva ◽

Maria V. Kuznetsova ◽

Olga V. Burmenskaya ◽

Andrey E. Donnikov ◽

Elena A. Kalinina

Keyword(s):

Gene Expression ◽

Transcriptome Profiling ◽

Endometrial Receptivity ◽

In Vitro Fertilisation ◽

Ivf Outcome ◽

Program Outcomes ◽

Implantation Window ◽

Genome Wide ◽

A Genome

Relevance. The success of the in vitro fertilisation (IVF) program, among other factors, depends on the readiness of the endometrium to accept the embryo. It is believed that this is possible during the so-called implantation window, the timing of which can be shifted under the influence of various factors. Evaluation of endometrial receptivity and the implantation window based on analysis of endometrial gene expression before embryo transfer is a promising approach for predicting the likelihood of pregnancy in IVF programs. Aim. To construct a classifier based on the expression of endometrial genes for predicting the outcome of an IVF program in patients with tubal-peritoneal infertility factor and repeated failed IVF attempts in history. Materials and methods. Before the IVF program, a genome-wide transcriptome profiling of endometrial samples of 15 women with tubal-perioneal infertility factor and repeated unsuccessful IVF attempts in history was carried out using Affymetrix arrays. Potential genes capable of classifying IVF program outcomes were selected, after which the expression of these genes was analyzed by qPCR-RT in the endometrium of 47 women to construct IVF outcome classifiers based on the expression of pairs or triples of genes. Results. A classifier based on the expression of the triple of genes MSX1 (HOX7), HOXA11, and TP53I3 made it possible to determine the onset of pregnancy in an IVF program with a sensitivity of 73% and a specificity of 71% with an area under the ROC-curve (AUC) of 0.738 (95% confidence interval 0.5770.898). Earlier, a relationship was found between the expression of these genes and receptivity of the endometrium, which suggests that these genes play a role in the onset of the implantation window. Conclusions. The use of a classifier based on the genes MSX1 (HOX7), HOXA11, and TP53I3 can determine the readiness of the endometrium to accept an embryo and create an individual prognosis of the outcome of an IVF program in women with tubal-peritoneal infertility factor and repeated failed IVF attempts in history.

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Genome-wide identification and comparative evolutionary analysis of the Dof transcription factor family in physic nut and castor bean

PeerJ ◽

10.7717/peerj.6354 ◽

2019 ◽

Vol 7 ◽

pp. e6354 ◽

Cited By ~ 6

Author(s):

Zhi Zou ◽

Xicai Zhang

Keyword(s):

Transcription Factor ◽

Stress Responses ◽

Castor Bean ◽

Ricinus Communis ◽

Transcriptome Profiling ◽

Evolutionary Analysis ◽

Physic Nut ◽

Transcription Factor Family ◽

Genome Wide ◽

A Genome

DNA-binding with one finger (Dof) proteins comprise a plant-specific transcription factor family involved in plant growth, development and stress responses. This study presents a genome-wide comparison of Dof family genes in physic nut (Jatropha curcas) and castor bean (Ricinus communis), two Euphorbiaceae plants that have not experienced any recent whole-genome duplication. A total of 25 or 24 Dof genes were identified from physic nut and castor genomes, respectively, where JcDof genes are distributed across nine out of 11 chromosomes. Phylogenetic analysis assigned these genes into nine groups representing four subfamilies, and 24 orthologous groups were also proposed based on comparison of physic nut, castor, Arabidopsis and rice Dofs. Conserved microsynteny was observed between physic nut and castor Dof-coding scaffolds, which allowed anchoring of 23 RcDof genes to nine physic nut chromosomes. In contrast to how no recent duplicate was present in castor, two tandem duplications and one gene loss were found in the Dof gene family of physic nut. Global transcriptome profiling revealed diverse patterns of Jc/RcDof genes over various tissues, and key Dof genes involved in flower development and stress response were also identified in physic nut. These findings provide valuable information for further studies of Dof genes in physic nut and castor.

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Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy

10.1101/284240 ◽

2018 ◽

Author(s):

Avinash Das ◽

Joo Sang Lee ◽

Gao Zhang ◽

Zhiyong Wang ◽

Ramiro Iglesias-Bartolome ◽

...

Keyword(s):

Cancer Cells ◽

Cancer Patients ◽

Targeted Therapies ◽

Survival Data ◽

Therapy Resistance ◽

Molecular Events ◽

Genome Wide ◽

A Genome ◽

Melanoma Patients ◽

Targeted Gene Inactivation

ABSTRACTMost patients with advanced cancer eventually acquire resistance to targeted therapies, spurring extensive efforts to identify molecular events mediating therapy resistance. Many of these events involvesynthetic rescue (SR) interactions, where the reduction in cancer cell viability caused by targeted gene inactivation is rescued by an adaptive alteration of another gene (therescuer). Here we perform a genome-wide prediction of SR rescuer genes by analyzing tumor transcriptomics and survival data of 10,000 TCGA cancer patients. Predicted SR interactions are validated in new experimental screens. We show that SR interactions can successfully predict cancer patients’ response and emerging resistance. Inhibiting predicted rescuer genes sensitizes resistant cancer cells to therapies synergistically, providing initial leads for developing combinatorial approaches to overcome resistance proactively. Finally, we show that the SR analysis of melanoma patients successfully identifies known mediators of resistance to immunotherapy and predicts novel rescuers.

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Slc7a8 deletion is protective against diet-induced obesity and attenuates lipid accumulation in multiple organs

10.1101/2021.10.25.465668 ◽

2021 ◽

Author(s):

Reabetswe Pitere ◽

Marlene van Heerden ◽

Michael Sean Pepper ◽

Melvin Anyasi Ambele

Keyword(s):

Lipid Accumulation ◽

Control Diet ◽

Multiple Organs ◽

Diet Induced Obesity ◽

Genome Wide ◽

A Genome ◽

Brown Adipose ◽

Adipocyte Hyperplasia ◽

Stromal Stem Cells

Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of adipogenesis in human adipose derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel mediator. This study has investigated the role of SLC7A8 in adipose tissue biology using a mouse model of diet-induced obesity. slc7a8 knockout (KO) and wildtype (WT) C57BL/6J mice were fed either a control diet (CD) or a high-fat diet (HFD) for 14 weeks. On HFD, both WT and KO (WTHFD and KOHFD) gained significantly more weight than their CD counterparts. However, KOHFD gained significantly less weight than WT HFD. KOHFD significantly reduced the level of glucose intolerance observed in WTHFD. KOHFD significantly reduced both adipocyte mass and hypertrophy in inguinal, mesenteric, perigonadal and brown adipose depots, with a corresponding decrease in macrophage infiltration. Additionally, KOHFD decreased lipid accumulation in the liver, heart, gastrocnemius muscle, lung, and kidney. This study demonstrates that targeting SLC7A8 protects against diet-induced obesity by reducing lipid accumulation in multiple organs, and thereby has the potential to mitigate the development of obesity-associated comorbidities.

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Temporal transcriptome profiling of Microchloropsis gaditana CCMP526 under hyper-saline conditions

10.1101/2020.06.07.139238 ◽

2020 ◽

Author(s):

Anbarasu Karthikaichamy ◽

John Beardall ◽

Ross Coppel ◽

Santosh Noronha ◽

Sanjeeva Srivastava ◽

...

Keyword(s):

Regulatory Networks ◽

Carbon Assimilation ◽

Transcriptome Profiling ◽

Transcript Abundance ◽

Membrane Lipid ◽

Genome Wide ◽

A Genome ◽

Wide Range ◽

Salinity Levels ◽

Inducible Genes

ABSTRACTMicroalgae can tolerate a wide range of environmental conditions and have been exploited for their lipid and carbohydrate accumulating properties. The utility of this process could be further enhanced through understanding the critical gene regulatory networks that govern the acclimatization process. Advancements in systems biology and sequencing tools now enable us to obtain a genome-wide overview of gene expression under particular conditions of interest. Under salinity stress, Microchloropsis gaditana CCMP526, a commercially important alga has been previously reported to accumulate carbohydrate and lipid. To understand the mechanism of acclimatization, here we report a temporal transcriptomic analysis of M. gaditana under two different salinity levels (55 and 100 PSU). The short term (0, 1 and 6 h) and long term (24 and 72 h) responses of the salt-induced transcript pool were used to identify salinity-inducible genes using correspondence analysis. The transcript abundance of genes involved in triacylglycerol biosynthesis, membrane lipid modification, carbon assimilation and shunting, and osmolyte biosynthesis indicated that M. gaditana employs a two-stage acclimatization strategy during hypersaline conditions.

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