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- Agalou, Adamantia, et al.
(author)
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A genome-wide survey of HD-Zip genes in rice and analysis of drought-responsive family members
- 2008
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In: Plant Molecular Biology. - : Springer Science and Business Media LLC. - 0167-4412 .- 1573-5028. ; 66:1-2, s. 87-103
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Journal article (peer-reviewed)abstract
- The homeodomain leucine zipper (HD-Zip) genes encode transcription factors that have diverse functions in plant development and have often been implicated in stress adaptation. The HD-Zip genes are the most abundant group of homeobox (HB) genes in plants and do not occur in other eukaryotes. This paper describes the complete annotation of the HD-Zip families I, II and III from rice and compares these gene families with Arabidopsis in a phylogeny reconstruction. Orthologous pairs of rice and Arabidopsis HD-Zip genes were predicted based on neighbour joining and maximum parsimony (MP) trees with support of conserved intron-exon organization. Additionally, a number of HD-Zip genes appeared to be unique to rice. Searching of EST and cDNA databases and expression analysis using RT-PCR showed that 30 out of 31 predicted rice HD-Zip genes are expressed. Most HD-Zip genes were broadly expressed in mature plants and seedlings, but others showed more organ specific patterns. Like in Arabidopsis and other dicots, a subset of the rice HD-Zip I and II genes was found to be regulated by drought stress. We identified both drought-induced and drought-repressed HD-Zip genes and demonstrate that these genes are differentially regulated in drought-sensitive versus drought-tolerant rice cultivars. The drought-repressed HD-Zip family I gene, Oshox4, was selected for promoter-GUS analysis, showing that drought-responsiveness of Oshox4 is controlled by the promoter and that Oshox4 expression is predominantly vascular-specific. Loss-of-function analysis of Oshox4 revealed no specific phenotype, but overexpression analysis suggested a role for Oshox4 in elongation and maturation processes.
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- Lindqvist, C. Mårten, et al.
(author)
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Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes
- 2016
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:39, s. 64071-64088
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Journal article (peer-reviewed)abstract
- To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.
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- Lindqvist, C Mårten, et al.
(author)
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The Mutational Landscape in Pediatric Acute Lymphoblastic Leukemia Deciphered by Whole Genome Sequencing
- 2015
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In: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 36:1, s. 118-128
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Journal article (peer-reviewed)abstract
- Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.
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- Lysenkova Wiklander, Mariya, et al.
(author)
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Genomic, transcriptomic and epigenomic sequencing data of the B-cell leukemia cell line REH
- 2023
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In: BMC Research Notes. - : BioMed Central (BMC). - 1756-0500. ; 16:1
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Journal article (peer-reviewed)abstract
- ObjectivesThe aim of this data paper is to describe a collection of 33 genomic, transcriptomic and epigenomic sequencing datasets of the B-cell acute lymphoblastic leukemia (ALL) cell line REH. REH is one of the most frequently used cell lines for functional studies of pediatric ALL, and these data provide a multi-faceted characterization of its molecular features. The datasets described herein, generated with short- and long-read sequencing technologies, can both provide insights into the complex aberrant karyotype of REH, and be used as reference datasets for sequencing data quality assessment or for methods development.Data descriptionThis paper describes 33 datasets corresponding to 867 gigabases of raw sequencing data generated from the REH cell line. These datasets include five different approaches for whole genome sequencing (WGS) on four sequencing platforms, two RNA sequencing (RNA-seq) techniques on two different sequencing platforms, DNA methylation sequencing, and single-cell ATAC-sequencing.
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- Nordlund, Jessica, et al.
(author)
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DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia
- 2015
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In: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7083 .- 1868-7075. ; 7
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Journal article (peer-reviewed)abstract
- Background: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA methylation as a complement to current diagnostic methods. A secondary aim was to gain insight into the functional role of DNA methylation in ALL. Results: We used the methylation status of similar to 450,000 CpG sites in 546 well-characterized patients with T-ALL or seven recurrent B-cell precursor ALL subtypes to design and validate sensitive and accurate DNA methylation classifiers. After repeated cross-validation, a final classifier was derived that consisted of only 246 CpG sites. The mean sensitivity and specificity of the classifier across the known subtypes was 0.90 and 0.99, respectively. We then used DNA methylation classification to screen for subtype membership of 210 patients with undefined karyotype (normal or no result) or non-recurrent cytogenetic aberrations('other' subtype). Nearly half (n = 106) of the patients lacking cytogenetic subgrouping displayed highly similar methylation profiles as the patients in the known recurrent groups. We verified the subtype of 20% of the newly classified patients by examination of diagnostic karyotypes, array-based copy number analysis, and detection of fusion genes by quantitative polymerase chain reaction (PCR) and RNA-sequencing (RNA-seq). Using RNA-seq data from ALL patients where cytogenetic subtype and DNA methylation classification did not agree, we discovered several novel fusion genes involving ETV6, RUNX1, and PAX5. Conclusions: Our findings indicate that DNA methylation profiling contributes to the clarification of the heterogeneity in cytogenetically undefined ALL patient groups and could be implemented as a complementary method for diagnosis of ALL. The results of our study provide clues to the origin and development of leukemic transformation. The methylation status of the CpG sites constituting the classifiers also highlight relevant biological characteristics in otherwise unclassified ALL patients.
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- Shao, Jingxia, et al.
(author)
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Functional analysis of the HD-Zip transcription factor genes Oshox12 and Oshox14 in rice
- 2018
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:7
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Journal article (peer-reviewed)abstract
- The homeodomain-leucine zipper (HD-Zip) transcription factor family plays vital roles in plant development and morphogenesis as well as responses to biotic and abiotic stresses. In barley, a recessive mutation in Vrs1 (HvHox1) changes two-rowed barley to six-rowed barley, which improves yield considerably. The Vrs1 gene encodes an HD-Zip subfamily I transcription factor. Phylogenetic analysis has shown that the rice HD-Zip I genes Oshox12 and Oshox14 are the closest homologues of Vrs1. Here, we show that Oshox12 and Oshox14 are ubiquitously expressed with higher levels in developing panicles. Trans-activation assays in yeast and rice protoplasts demonstrated that Oshox12 and Oshox14 can bind to a specific DNA sequence, AH1 (CAAT(A/T)ATTG), and activate reporter gene expression. Overexpression of Oshox12 and Oshox14 in rice resulted in reduced panicle length and a dwarf phenotype. In addition, Oshox14 overexpression lines showed a deficiency in panicle exsertion. Our findings suggest that Oshox12 and Oshox14 may be involved in the regulation of panicle development. This study provides a significant advancement in understanding the functions of HD-Zip transcription factors in rice.
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- Valdés, Ana Elisa, et al.
(author)
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The homeodomain-leucine zipper (HD-Zip) class I transcription factors ATHB7 and ATHB12 modulate abscisic acid signalling by regulating protein phosphatase 2C and abscisic acid receptor gene activities
- 2012
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In: Plant Molecular Biology. - : Springer Science and Business Media LLC. - 0167-4412 .- 1573-5028. ; 80:4-5, s. 405-418
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Journal article (peer-reviewed)abstract
- Plants perceiving drought activate multiple responses to improve survival, including large-scale alterations in gene expression. This article reports on the roles in the drought response of two Arabidopsis thaliana homeodomain-leucine zipper class I genes; ATHB7 and ATHB12, both strongly induced by water-deficit and abscisic acid (ABA). ABA-mediated transcriptional regulation of both genes is shown to depend on the activity of protein phosphatases type 2C (PP2C). ATHB7 and ATHB12 are, thus, targets of the ABA signalling mechanism defined by the PP2Cs and the PYR/PYL family of ABA receptors, with which the PP2C proteins interact. Our results from chromatin immunoprecipitation and gene expression analyses demonstrate that ATHB7 and ATHB12 act as positive transcriptional regulators of PP2C genes, and thereby as negative regulators of abscisic acid signalling. In support of this notion, our results also show that ATHB7 and ATHB12 act to repress the transcription of genes encoding the ABA receptors PYL5 and PYL8 in response to an ABA stimulus. In summary, we demonstrate that ATHB7 and ATHB12 have essential functions in the primary response to drought, as mediators of a negative feedback effect on ABA signalling in the plant response to water deficit.
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12. |
- Övernäs, Elin, 1978-
(author)
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Characterisation of Members of the HD-Zip I and DREB/ERF Transcription Factor Families and their Functions in Plant Stress Responses
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Plants have to adapt to various environmental conditions. In comparison with other eukaryotes, plant genomes encode relatively many transcription factors, and have families of transcription factors only found in plants, two such are the large AP2/ERF (APETALA2/Ethylene Responsive Factor) and HD-Zip (Homeodomain leucine zipper) families. Members of these families play roles in plant development, responses to stress and other environmental stimuli. This thesis describes the functions of members of both these families. Two AP2/ERF proteins of the DREB/ERF (Drought Responsive Element Binding/Ethylene Responsive Factor) subfamily, AtERF38 and AtERF39 show a negative effect on growth in transgenic over-expression lines. They are regulated by stress and confer stress tolerance, which suggests a function as negative growth regulators during stress. The 14 Oryza sativa (rice) HD-Zip I genes were described and a phylogenetic analysis of the HD-Zip I genes in Arabidopsis thaliana, rice and Craterostigma plantagineum defined four clades that were conserved between mono and dicots, but also showed that four clades had most likely been lost in either lineage. The phylogeny was supported by conserved intron/exon patterning and the duplication history of the rice genome. The expression patterns in different organs indicate a non-conserved regulation of genes within and between clades. Drought stress regulation was conserved within two clades, but not between the clades. Further analysis on the function of four HD-Zip I genes in Arabidopsis, ATHB5, -6, -7 and -12 showed an involvement in the transcriptional regulation of ABA receptors and signalling components. These are the first described direct target genes for ATHB7 and ATHB12. It was also shown that there exists a direct cross-regulation between these four HD-Zips. The effect of ATHB5, -6, -7 and -12 would be as negative regulators of ABA signalling, desensitising the plant to constant levels of ABA, and enabling sensitivity to changes in stress level.
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