Progressive dosage compensation during
            <i>Drosophila</i>
            embryogenesis is reflected by gene arrangement

Prayitno, Khairunnadiya; Schauer, Tamás; Regnard, Catherine; Becker, Peter B.

doi:10.15252/embr.201948138

Cited by 13 publications

(22 citation statements)

References 39 publications

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“…3 a). For histone acetylation, studies have found that the acetylation level in model organisms of monosomy 5 and monosomy 45, X is elevated [42,43], which provides supporting evidence for our ndings.…”

Section: Discussionsupporting

confidence: 87%

Are there common mechanisms of aneuploidy-related abortion and defects in fetus?

Xie

Lü

Huang

et al. 2020

Preprint

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Background: Monosomies and trisomies, as the most common aneuploid abnormalities, are the leading causes of miscarriages and fetal defects in humans. Although there is evidence suggested that aneuploid may have some common aspects, their common mechanism still remains unclear. This studies objective was to explore the common mechanism of monosomies and trisomies, with a purpose to identify some critical biomarkers and pathway so as to early diagnosis and effective therapy.Methods: We obtained the mRNA expression profile of GSE114559 including 101 samples data from GEO database. These data include normal, every monosomic, and trisomic transcriptome. We conducted Limma analysis by using the adj. p<0.05 and |FC|>1 criteria to identify all monosomy-related, trisomy-related differentially expressed genes (DEGs), and also to found their overlapping DEGs through Venn diagram. We then performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses, protein-protein interaction(PPI) network analysis to find the functional, pathways and hub genes in these DEGs. We carried out weighted correlation network analysis (WGCNA) to further detect the candidate genes and pathways related to all DEGs and their overlappling DEGs. Finally, we further used qPCR to certify pathological change of specific genes. Results: We identified all monosomy-related, trisomy-related DEGs, and their overlapping DEGs which were enriched by spliceosome, thyroid hormone, infection-related genes and signalling pathways. We also found that epigenetic related pathways were significantly enriched in the DEGs of monosomies by GO, KEGG. We explode the hub gene and module in the DEGs of monosomies and the overlapping DEGs by PPI. Then, we found that spliceosome, thyroid hormone, infection-related genes and signalling pathways were enriched in all DEGs group and the overlapping DEGs group by weighted correlation network analysis (WGCNA). Finally, we certified some hub gene in the trisomy 21, 47, XYY samples from clinical patients by qPCR which were consistent with results of PPI analysis.Conclusion: Our study indicates the potential common mechanism underlining spliceosome, thyroid hormone and infection-related signalling pathways for both monosomies and trisomies, and the mechanism underling epigenetic for monosomies.

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Section: Discussionsupporting

confidence: 87%

Are there common mechanisms of aneuploidy-related abortion and defects in fetus?

Xie

Lü

Huang

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…We speculate that roX1 may integrate via a different mechanism or via an unknown co-factor. Alternatively, roX1 may have a different role during the process of dosage compensation early in development as suggested by a recent study ( 69 ).…”

Section: Discussionmentioning

confidence: 86%

Two-step mechanism for selective incorporation of lncRNA into a chromatin modifier

Müller

Schauer

Krause

et al. 2020

Nucleic Acids Research

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The MLE DExH helicase and the roX lncRNAs are essential components of the chromatin modifying Dosage Compensation Complex (DCC) in Drosophila. To explore the mechanism of ribonucleoprotein complex assembly, we developed vitRIP, an unbiased, transcriptome-wide in vitro assay that reveals RNA binding specificity. We found that MLE has intrinsic specificity for U-/A-rich sequences and tandem stem-loop structures and binds many RNAs beyond roX in vitro. The selectivity of the helicase for physiological substrates is further enhanced by the core DCC. Unwinding of roX2 by MLE induces a highly selective RNA binding surface in the unstructured C-terminus of the MSL2 subunit and triggers-specific association of MLE and roX2 with the core DCC. The exquisite selectivity of roX2 incorporation into the DCC thus originates from intimate cooperation between the helicase and the core DCC involving two distinct RNA selection principles and their mutual refinement.

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“…Yet, the relationship between CLAMP and GAF in early embryos remains unknown. It is very possible that the competitive relationship has not been established in early embryos, since dosage compensation has not yet been initiated (Prayitno et al, 2019). Moreover, the GA-rich sequences targeted by CLAMP and GAF are distinct in vivo and in vitro .…”

Section: Discussionmentioning

confidence: 99%

“…Drosophila embryos initiate X chromosome counting in NC12 and start the sex determination cascade piror to the major wave of ZGA at NC14 (Gergen, 1987; Bosch et al, 2006). However, the majority of dosage compensation initiates much later in embryonic development (Prayitno et al, 2019). Therefore, our data support a model in which CLAMP functions early in the embryo prior to MSL complex assembly to open up specific chromatin regions for MSL complex recruitment later (J.…”

Section: Discussionmentioning

confidence: 99%

CLAMP and Zelda function together to promote Drosophila zygotic genome activation

Duan

Rieder

Colonnetta

et al. 2020

Preprint

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Because zygotic genome activation (ZGA) is an essential process across metazoans, it is key to evolve multiple pioneer transcription factors (TFs) to protect organisms from loss of a single factor. Pioneer TF Zelda (ZLD) is the only known factor which increases accessibility of chromatin to promote ZGA in the early Drosophila embryo. However, many genomic loci remain accessible without ZLD and have GA-rich motifs. Therefore, we hypothesized that other pioneer TFs that function with ZLD have not yet been identified in early embryos, especially those that bind to GA-rich motifs, such as CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins). Here, we determine that CLAMP is a novel pioneer TF which interacts directly with nucleosomes, regulates zygotic genome transcription, promotes chromatin accessibility, and facilitates the binding of ZLD to promoters. Thus, the maternal factor CLAMP functions with ZLD as a pioneer TF to open chromatin and drive zygotic genome activation.

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Progressive dosage compensation during Drosophila embryogenesis is reflected by gene arrangement

Cited by 13 publications

References 39 publications

Are there common mechanisms of aneuploidy-related abortion and defects in fetus?

Are there common mechanisms of aneuploidy-related abortion and defects in fetus?

Two-step mechanism for selective incorporation of lncRNA into a chromatin modifier

CLAMP and Zelda function together to promote Drosophila zygotic genome activation

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