Biology subjects

Gao, Y. Z.

Publications and source records attributed to Gao, Y. Z..

2 recordsLinked to original sources

bioRxiv2026

Polymorphic 3D genome architecture mediated by transposable elements

The three-dimensional (3D) folding of the genome plays a crucial role in genome regulation. However, how 3D genome structure varies between individuals and consequently influences genome function and evolution remains poorly understood. One potential source of this variation is transposable elements (TEs), genomic parasites whose location and composition vary between species and individuals. Hosts typically silence TEs through enriching them with repressive epigenetic marks, turning euchromatic TEs into heterochromatin islands, which were shown to spatially interact with pericentromeric heterochromatin (PCH). Because most TE insertions are present in only a few individuals within Drosophila populations, we asked whether polymorphism in the presence/absence of TEs drives varying 3D structures through TE-PCH spatial interactions. We performed deep-coverage Hi-C of two wild-type Drosophila strains and developed a Hi-C analysis framework enabling allelic comparisons of spatial interactions with PCH. Supporting our hypothesis, nearly 40% of strain-specific euchromatic TEs cause their adjacent euchromatic regions to be spatially closer to PCH than TE-free homologous alleles. These interactions are not limited to specific TE families, and, surprisingly, telomere-proximal TEs show a similar propensity as centromere-proximal TEs to enhance PCH interactions. The most defining feature of TEs involved in PCH interactions is H3K9me3 enrichment, revealing a chromatin-based mechanism for TE-mediated 3D genome organization broadly applicable across TE families and genome locations. Importantly, TEs involved in PCH interactions reduce the expression of adjacent genes and are evolutionarily young, indicating stronger selection against them. Our study reveals a previously uncharacterized mechanism by which TEs influence the function and evolution of host genomes by generating polymorphic 3D genome organization.

genomics↗

bioRxiv2024

Alternative splicing of clock transcript mediates the response of circadian clocks to temperature changes

Circadian clocks respond to temperature changes over the calendar year, allowing organisms to adjust their daily biological rhythms to optimize health and fitness. In Drosophila, seasonal adaptations and temperature compensation are regulated by temperature-sensitive alternative splicing (AS) of period (per) and timeless (tim) genes that encode key transcriptional repressors of clock gene expression. Although clock (clk) gene encodes the critical activator of clock gene expression, AS of its transcripts and its potential role in temperature regulation of clock function have not been explored. We therefore sought to investigate whether clk exhibits AS in response to temperature and the functional changes of the differentially spliced transcripts. We observed that clk transcripts indeed undergo temperature-sensitive AS. Specifically, cold temperature leads to the production of an alternative clk transcript, hereinafter termed clk-cold, which encodes a CLK isoform with an in-frame deletion of four amino acids proximal to the DNA binding domain. Notably, serine 13 (S13), which we found to be a CK1-dependent phosphorylation site, is among the four amino acids deleted in CLK-cold protein. Using a combination of transgenic fly, tissue culture, and in vitro experiments, we demonstrated that upon phosphorylation at CLK(S13), CLK-DNA interaction is reduced, thus decreasing CLK occupancy at clock gene promoters. This is in agreement with our findings that CLK occupancy at clock genes and transcriptional output are elevated at cold temperature, which can be explained by the higher amounts of CLK-cold isoforms that lack S13 residue. This study provides new insights into the complex collaboration between AS and phospho-regulation in shaping temperature responses of the circadian clock.

neuroscience↗