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Parent-of-origin effects on nuclear chromatin organization and behavior in Drosophila model of Williams-Beuren Syndrome.

ABSTRACT: Development of prognostic models for neuropsychiatric disorders requires careful consideration of individual 1) parent-of-origin effects (POEs) relying on 2) nuclear 3D chromatin architecture of the nerve cells and 3) epigenetic impact of miRNAs produced in parental germ cells. The interplay of these events in shaping cognitive phenotypes in progeny is far from clear. Simple experimental model systems such as Drosophila can help to probe the causes and consequences leading to human neuropathology. Recently, we have developed a Drosophila model for Williams-Beuren Syndrome (WBS) – a mutant agnts3 of the agnostic locus (X:11AB) harboring limk1 gene for the key enzyme of actin remodeling LIM-kinase1. The mutation agnts3 drastically increases frequency of ectopic contacts (FEC) in specific regions of intercalary heterochromatin, suppresses learning acquisition and memory formation and affects locomotion. This study reveals that in reciprocal hybrids between agnts3 and the wild type strain Berlin the polytene chromosome bands are heterogeneous in manner of FEC regulation depending either on maternal or paternal gene origin. Bioinformatic analysis demonstrates that FEC between X:11AB and the other bands of the X chromosome partly depends on short (~ 30 bp) identical DNA fragments homologous to Drosophila 372 bp satellite DNA repeats. Although learning acquisition in conditioned courtship suppression paradigm is similar in hybrids, the middle-term memory formation shows patroclinic inheritance. Seemingly, this depends on changes in miR-974 expression levels. Several parameters of locomotion demonstrate heterosis. Our data indicate that agnts3 locus is capable of trans-regulating gene activity via POEs on chromatin nuclear organization, thereby affecting behavioral quantitative traits.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE150980 | GEO | 2020/05/22

REPOSITORIES: GEO

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Project description:Friable embryogenic callus (FEC) has been considered as the most suitable materials for efficient genetic transformation of cassava. Due to heavy genotype dependence on FEC induction and being amenable to somaclonal variation, the production and maintaining of reliable FEC is a limitation factor for cassava genetic transformation. Identification of key elements involving in biological processes from somatic embryos (SEs) to the FEC at different stages will provide critical insights for FEC improvement. Cytological observation showed the dramatic change of subcellular structures among SEs, fresh FEC (FFEC) and old FEC (OFEC). Decrease of sucrose and increase of fructose and glucose were detected in OFEC. A total of 6871 differentially expressed genes (DEGs) were identified from SEs, FFEC and OFEC by RNA-seq. Analysis of the DEGs showed that FEC induction was accompanied by the process of dedifferentiation, whereas the epigenetics modification occurred during the continuous subculturing process. The cell structure was reconstructed, mainly including the GO terms of "cell periphery" and "external encapsulating structure"; in parallel, the internal mechanisms were changed correspondingly, including the metabolisms of process (glycolysis) and compounds(alanine, aspartate, and glutamate). The significant reduction of genomic DNA methylation in OFEC indicates altered gene expression via chromatin modification. These results indicate that the induction and long-term subculture of FEC is a complicated biological process involving changes of genome modification, gene expression and subcellular reconstruction. The findings will be useful for improving FEC induction and maintenance from farmer-preferred cassava cultivars that are recalcitrant to genetic transformation, hence improving cassava through genetic engineering. Two-week-old SEs cultured on GD, FFEC emerging from SEs, and 9-month-old OFEC were used for analysis. Each sample was mixtured from six indepedent replicates and were collected for RNA extraction respectively.

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Parent-of-origin effects on nuclear chromatin organization and behavior in Drosophila model of Williams-Beuren Syndrome.

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