scholarly journals The lncRNA EPB41L4A-AS1 regulates gene expression in the nucleus and exerts cell type-dependent effects on cell cycle progression

2021 ◽  
Author(s):  
Helle Samdal ◽  
Siv Anita Hegre ◽  
Konika Chawla ◽  
Nina-Beate Liabakk ◽  
Per Arne Aas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Phase Distribution ◽  
Cell Types ◽  
Metabolic Reprogramming ◽  
Cycle Phase ◽  
Cell Type ◽  
Chip Sequencing ◽  
Cell Cycle Phase Distribution

AbstractThe long non-coding RNA (lncRNA) EPB41L4A-AS1 is aberrantly expressed in various cancers and has been reported to be involved in metabolic reprogramming and as a repressor of the Warburg effect. Although the biological relevance of EPB41L4A-AS1 is evident, its functional role seems to vary depending on cell type and state of disease. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we previously identified EPB41L4A-AS1 to be one of 59 lncRNAs with potential cell cycle functions. Here, we demonstrate that EPB41L4A-AS1 exists as bright foci and regulates gene expression in the nucleus in both cis and trans. Specifically, we find that EPB41L4A-AS1 positively regulates its sense overlapping gene EPB41L4A and influences expression of hundreds of other genes, including genes involved in cell proliferation. Finally, we show that EPB41L4A-AS1 affects cell cycle phase distribution, though these effects vary between cell types.

scholarly journals The G2-phase enriched lncRNA SNHG26 is necessary for proper cell cycle progression and proliferation

2021 ◽  
Author(s):  
Helle Samdal ◽  
Siv A. Hegre ◽  
Konika Chawla ◽  
Nina-Beate Liabakk ◽  
Per A. Aas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Phase Distribution ◽  
Cell Cycle Phase ◽  
Cycle Phase ◽  
Cycle Progression ◽  
Chip Sequencing ◽  
Cell Cycle Phase Distribution ◽  
Regulation Of Cell Cycle

AbstractLong noncoding RNAs (lncRNAs) are involved in the regulation of cell cycle, although only a few have been functionally characterized. By combining RNA sequencing and ChIP sequencing of cell cycle synchronized HaCaT cells we have previously identified lncRNAs highly enriched for cell cycle functions. Based on a cyclic expression profile and an overall high correlation to histone 3 lysine 4 trimethylation (H3K4me3) and RNA polymerase II (Pol II) signals, the lncRNA SNHG26 was identified as a top candidate. In the present study we report that downregulation of SNHG26 affects mitochondrial stress, proliferation, cell cycle phase distribution, and gene expression in cis- and in trans, and that this effect is reversed by upregulation of SNHG26. We also find that the effect on cell cycle phase distribution is cell type specific and stable over time. Results indicate an oncogenic role of SNHG26, possibly by affecting cell cycle progression through the regulation of downstream MYC-responsive genes.

scholarly journals Characterizing and inferring quantitative cell cycle phase in single-cell RNA-seq data analysis

2019 ◽  
Author(s):  
Chiaowen Joyce Hsiao ◽  
PoYuan Tung ◽  
John D. Blischak ◽  
Jonathan E. Burnett ◽  
Kenneth A. Barr ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Single Cell ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Cell Cycle Phase ◽  
Cellular Heterogeneity ◽  
Cycle Phase ◽  
Cycle Progression ◽  
Cellular Environment

AbstractCellular heterogeneity in gene expression is driven by cellular processes such as cell cycle and cell-type identity, and cellular environment such as spatial location. The cell cycle, in particular, is thought to be a key driver of cell-to-cell heterogeneity in gene expression, even in otherwise homogeneous cell populations. Recent advances in single-cell RNA-sequencing (scRNA-seq) facilitate detailed characterization of gene expression heterogeneity, and can thus shed new light on the processes driving heterogeneity. Here, we combined fluorescence imaging with scRNA-seq to measure cell cycle phase and gene expression levels in human induced pluripotent stem cells (iPSCs). Using these data, we developed a novel approach to characterize cell cycle progression. While standard methods assign cells to discrete cell cycle stages, our method goes beyond this, and quantifies cell cycle progression on a continuum. We found that, on average, scRNA-seq data from only five genes predicted a cell’s position on the cell cycle continuum to within 14% of the entire cycle, and that using more genes did not improve this accuracy. Our data and predictor of cell cycle phase can directly help future studies to account for cell-cycle-related heterogeneity in iPSCs. Our results and methods also provide a foundation for future work to characterize the effects of the cell cycle on expression heterogeneity in other cell types.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

AbstractChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

scholarly journals Histone modifications form a cell-type-specific chromosomal bar code that modulates and maintains patterns of gene expression through the cell cycle

2020 ◽  
Author(s):  
John A. Halsall ◽  
Simon Andrews ◽  
Felix Krueger ◽  
Charlotte E. Rutledge ◽  
Gabriella Ficz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Histone Modifications ◽  
Expression Patterns ◽  
Cell Types ◽  
Cell Type ◽  
Bar Code ◽  
Genes Encoding ◽  
Cell Type Specific ◽  
Rolling Windows

ABSTRACTBackgroundChromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear.To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL) to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3.ResultsChromosome regions (bands) of 10-50Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. We show that they comprise 1-5Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely.We found little change between cell cycle phases, whether compared by 5Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains.Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription.ConclusionsModified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.

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