HP1B is a euchromatic Drosophila HP1 homolog with links to metabolism

Heterochromatin Protein 1 (HP1) proteins are an important family of chromosomal proteins conserved among all major eukaryotic lineages. While HP1 proteins are best known for their role in heterochromatin, many HP1 proteins function in euchromatin as well. As a group, HP1 proteins carry out diverse functions, playing roles in the regulation of gene expression, genome stability, chromatin structure, and DNA repair. While the heterochromatic HP1 proteins are well studied, our knowledge of HP1 proteins with euchromatic distribution is lagging behind. We have created the first mutations in HP1B, a Drosophila HP1 protein with euchromatic function, and the Drosophila homolog most closely related to mammalian HP1α, HP1β, and HP1γ. We find that HP1B is a non-essential protein in Drosophila, with mutations affecting fertility and animal activity levels. In addition, animals lacking HP1B show altered food intake and higher body fat levels. Gene expression analysis of animals lacking HP1B demonstrates that genes with functions in various metabolic processes are affected primarily by HP1B loss. Our findings suggest that there is a link between the chromatin protein HP1B and the regulation of metabolism.异染色质蛋白1（Heterochromatin Protein 1，HP1）家族是一类保守分布于所有主要真核生物谱系的重要染色体蛋白家族。尽管HP1蛋白因在异染色质中的经典功能被广泛研究，但诸多家族成员同样在常染色质中发挥生物学作用。作为一个整体蛋白家族，HP1具备多样的功能范式，参与基因表达调控、基因组稳定性维持、染色质结构重塑及DNA修复等核心生命过程。目前异染色质定位的HP1蛋白已被充分解析，但针对常染色质分布的HP1蛋白，学界的认知仍存在明显滞后。我们首次构建了HP1B的突变体：HP1B是一种兼具常染色质功能的果蝇HP1蛋白，同时也是与哺乳动物HP1α、HP1β及HP1γ亲缘关系最为接近的果蝇同源蛋白。研究发现，HP1B在果蝇中并非必需蛋白，其突变可影响果蝇的生育能力与活动水平。此外，HP1B缺失的果蝇还表现出进食量异常及体脂水平升高的表型。对HP1B缺失果蝇的基因表达分析显示，参与各类代谢过程的基因的表达主要受HP1B缺失的调控。本研究结果表明，染色质蛋白HP1B与代谢调控之间存在明确的功能关联。