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Zhuang, Q. K.-W.

Publications and source records attributed to Zhuang, Q. K.-W..

2 recordsLinked to original sources

Survey of gene, lncRNA and transposon transcription patterns in four mouse organs highlights shared and organ-specific sex-biased regulation

BackgroundSex-biased gene regulation is the basis of sexual dimorphism in phenotypes and has been studied across different cell types and different developmental stages. However, sex-biased expression of transposable elements (TEs) that represent nearly half of the mammalian genome and have the potential of influencing genome integrity and regulation, remains underexplored. ResultsHere, we report a survey of gene, lncRNA and TE expression in four organs from mice with different combinations of gonadal and genetic sex. Data show remarkable variability among organs with respect to the impact of gonadal sex on transcription with the strongest effects observed in liver. In contrast, the X-chromosome dosage alone had modest influence on sex-biased transcription across different organs, albeit interaction between X-dosage and gonadal sex cannot be ruled out. The presence of the Y chromosome influenced TE, but not gene or lncRNA expression in liver. Notably, 90% of sex-biased TEs (sDETEs) reside in clusters. Moreover, 54% of these clusters overlap or reside close (<100 kb) to sex-biased genes or lncRNAs, share the same sex bias, and also have higher expression levels than sDETE clusters that do not co-localize with other types of sex-biased transcripts. We also tested the heterochromatic sink hypothesis that predicts higher expression of TEs in XX individuals and found no evidence to support it. ConclusionsOur data show that sex-biased expression of TEs varies among organs with highest numbers of sDETEs found in liver following the trends observed for genes and lncRNAs. It is enhanced by proximity to other types of sex-biased transcripts.

genomics↗

ZMYM2 is essential for methylation of germline genes and active transposons in embryogenesis

ZMYM2 is a transcriptional repressor whose role in development is largely unexplored. We found that Zmym2-/- mice show embryonic lethality by E10.5. Molecular characterization of Zmym2-/- embryos revealed two distinct defects. First, they fail to undergo DNA methylation and silencing of germline gene promoters, resulting in widespread upregulation of germline genes. Second, they fail to methylate and silence the evolutionarily youngest and most active LINE element subclasses in mice. Zmym2-/- embryos show ubiquitous overexpression of LINE-1 protein as well as aberrant expression of transposon-gene fusion transcripts. Interaction and colocalization data indicate that ZMYM2 homes to germline genes via binding to the non-canonical polycomb complex PRC1.6 and to transposons via the TRIM28 complex. In the absence of ZMYM2, hypermethylation of histone 3 lysine 4 occurs at target sites, creating a chromatin landscape unfavourable for establishment of DNA methylation. ZMYM2-/- human embryonic stem cells also show aberrant upregulation and demethylation of young LINE elements, indicating a conserved role in repression of active transposons. ZMYM2 is thus an important new factor in DNA methylation patterning in early embryonic development.

molecular biology↗