Integrative analysis reveals functional and regulatory roles of H3K79me2 in mediating alternative splicing

Li, Tianbao; Liu, Qi; Garza, Nick; Kornblau, Steven M.; Jin, Victor X.

doi:10.1186/s13073-018-0538-1

Cited by 37 publications

(32 citation statements)

References 65 publications

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“…Neuro2a or U2OS cells Bioinformatics Data Analysis ChIP-seq data of ATF4 and RNA-seq data were collected from the Gene Expression Omnibus (GSE35681) (Han et al, 2013). Raw sequence reads were aligned against the human genomic sequence (GRCh37) using bowtie2 for ChIP-seq data and TopHat (version 2.0.14) for mRNA-seq data as previous described (Li et al, 2018;Liu et al, 2017). Only uniquely mapped reads were used for further downstream analysis.…”

Section: Star+methodsmentioning

confidence: 99%

The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4

Pathak

Liu

et al. 2019

Neuron

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Section: Star+methodsmentioning

confidence: 99%

The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4

Pathak

Liu

et al. 2019

Neuron

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“…In animals, both H3K79me2 and H3K36me3 are considered to be associated with active transcription [56][57][58], and more specifically transcript elongation, although conflicting evidence has been reported [47]. In addition, a role has been proposed for H3K79me2 in the regulation of alternative splicing [59], although again there is evidence to the contrary [48]. H3K79 methylation has not been detected in land plants [21].…”

Section: Epigenetic Regulation In a Multicellular Brown Algamentioning

confidence: 99%

Histone modifications during the life cycle of the brown algaEctocarpus

Bourdareau

Tirichine

Lombard

et al. 2020

Preprint

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Background: Brown algae evolved complex multicellularity independently of the animal and land plant lineages and are the third most developmentally complex phylogenetic group on the planet. An understanding of developmental processes in this group is expect to provide important insights into the evolutionary events necessary for the emergence of complex multicellularity. Here we have focused on mechanisms of epigenetic regulation involving posttranslational modifications (PTMs) of histone proteins. Results:A total of 45 histone PTMs were identified, including two novel marks, but Ectocarpus lacks both H3K27me3 and the major polycomb complexes. ChIP-seq identified PTMs associated with transcription start sites (TSSs) and gene bodies of active genes, and with transposons. H3K79me2 exhibited an unusual pattern, often marking large genomic regions spanning several genes. TSSs of closely spaced divergently transcribed gene pairs shared a common nucleosome depleted region and exhibited shared histone PTM peaks. Overall, patterns of histone PTMs were stable through the life cycle. Analysis of histone PTMs at generation-biased genes provided insights into their functions during gene induction. Conclusions:The overview of the nature and functions of histone PTMs in the brown algae presented here will provide a foundation for future studies aimed at understanding epigenetic processes in the brown algae.

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“…Li et al (2018) integrated AS events derived from RNA-seq with H3K79me2 ChIP-seq data across 34 human normal and cancer cell types [174]. Clustering based on skipping exon-associated sites divided all cell types to 6 clusters.…”

Section: Alternative Transcripts: Another Source Of Transcriptomementioning

confidence: 99%

Not Only Mutations Matter: Molecular Picture of Acute Myeloid Leukemia Emerging from Transcriptome Studies

Handschuh

2019

Journal of Oncology

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The last two decades of genome-scale research revealed a complex molecular picture of acute myeloid leukemia (AML). On the one hand, a number of mutations were discovered and associated with AML diagnosis and prognosis; some of them were introduced into diagnostic tests. On the other hand, transcriptome studies, which preceded AML exome and genome sequencing, remained poorly translated into clinics. Nevertheless, gene expression studies significantly contributed to the elucidation of AML pathogenesis and indicated potential therapeutic directions. The power of transcriptomic approach lies in its comprehensiveness; we can observe how genome manifests its function in a particular type of cells and follow many genes in one test. Moreover, gene expression measurement can be combined with mutation detection, as high-impact mutations are often present in transcripts. This review sums up 20 years of transcriptome research devoted to AML. Gene expression profiling (GEP) revealed signatures distinctive for selected AML subtypes and uncovered the additional within-subtype heterogeneity. The results were particularly valuable in the case of AML with normal karyotype which concerns up to 50% of AML cases. With the use of GEP, new classes of the disease were identified and prognostic predictors were proposed. A plenty of genes were detected as overexpressed in AML when compared to healthy control, includingKIT,BAALC,ERG,MN1,CDX2,WT1,PRAME,andHOXgenes. High expression of these genes constitutes usually an unfavorable prognostic factor. Upregulation ofFLT3andNPM1genes, independent on their mutation status, was also reported in AML and correlated with poor outcome. However, transcriptome is not limited to the protein-coding genes; other types of RNA molecules exist in a cell and regulate genome function. It was shown that microRNA (miRNA) profiles differentiated AML groups and predicted outcome not worse than protein-coding gene profiles. For example, upregulation ofmiR-10a,miR-10b, andmiR-196band downregulation ofmiR-192were found as typical of AML withNPM1mutation whereas overexpression ofmiR-155was associated withFLT3-internal tandem duplication (FLT3-ITD). Development of high-throughput technologies and microarray replacement by next generation sequencing (RNA-seq) enabled uncovering a real variety of leukemic cell transcriptomes, reflected by gene fusions, chimeric RNAs, alternatively spliced transcripts, miRNAs, piRNAs, long noncoding RNAs (lncRNAs), and their special type, circular RNAs. Many of them can be considered as AML biomarkers and potential therapeutic targets. The relations between particular RNA puzzles and other components of leukemic cells and their microenvironment, such as exosomes, are now under investigation. Hopefully, the results of this research will shed the light on these aspects of AML pathogenesis which are still not completely understood.

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Integrative analysis reveals functional and regulatory roles of H3K79me2 in mediating alternative splicing

Cited by 37 publications

References 65 publications

The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4

The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4

Histone modifications during the life cycle of the brown algaEctocarpus

Not Only Mutations Matter: Molecular Picture of Acute Myeloid Leukemia Emerging from Transcriptome Studies

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