PDF(Pubmed)
Abstract：
Members of the diverse heterochromatin protein 1 (HP1) family play crucial roles in heterochromatin formation and maintenance. Despite the similar affinities of their chromodomains for di- and tri-methylated histone H3 lysine 9 (H3K9me2/3), different HP1 proteins exhibit distinct chromatin-binding patterns, likely due to interactions with various specificity factors. Previously, we showed that the chromatin-binding pattern of the HP1 protein Rhino, a crucial factor of the Drosophila PIWI-interacting RNA (piRNA) pathway, is largely defined by a DNA sequence-specific C2H2 zinc finger protein named Kipferl (Baumgartner et al., 2022). Here, we elucidate the molecular basis of the interaction between Rhino and its guidance factor Kipferl. Through phylogenetic analyses, structure prediction, and in vivo genetics, we identify a single amino acid change within Rhino\'s chromodomain, G31D, that does not affect H3K9me2/3 binding but disrupts the interaction between Rhino and Kipferl. Flies carrying the rhinoG31D mutation phenocopy kipferl mutant flies, with Rhino redistributing from piRNA clusters to satellite repeats, causing pronounced changes in the ovarian piRNA profile of rhinoG31D flies. Thus, Rhino\'s chromodomain functions as a dual-specificity module, facilitating interactions with both a histone mark and a DNA-binding protein.
摘要：
不同的异染色质蛋白1（HP1）家族成员在异染色质的形成和维持中起着至关重要的作用。尽管它们的染色体结构域对二和三甲基化组蛋白H3赖氨酸9（H3K9me2/3）具有相似的亲和力，不同的HP1蛋白表现出不同的染色质结合模式，可能是由于与各种特异性因素的相互作用。以前,我们发现HP1蛋白Rhino的染色质结合模式，果蝇PIWI相互作用RNA（piRNA）途径的关键因素，在很大程度上由一种名为Kipferl的DNA序列特异性C2H2锌指蛋白定义（Baumgartner等人。,2022年）。这里,我们阐明了Rhino与其指导因子Kipferl相互作用的分子基础。通过系统发育分析，结构预测，和体内遗传学，我们鉴定了Rhino的色域内的单个氨基酸变化，G31D,这不会影响H3K9me2/3结合，但会破坏Rhino和Kipferl之间的相互作用。携带rhinoG31D突变表型突变的苍蝇，犀牛从piRNA簇重新分配到卫星重复序列，引起rhinoG31D果蝇卵巢piRNA谱的明显变化。因此，犀牛的色域作为双特异性模块，促进与组蛋白标记和DNA结合蛋白的相互作用。
