Epigenomic conservation of transposable element silencing [ChIP-seq]

Transposable elements (TEs) comprise a substantial proportion of primate genomes. Because of the potential deleterious effects of TEs during development, TEs are targeted for silencing by sequence-specific KRAB-ZNF proteins, which recruit the TRIM28-SETDB1 complex, to deposit the repressive histone modification H3K9me3. TEs, in turn, acquire mutations to evade detection by the host, and hence KRAB-ZNF proteins need to rapidly evolve to counteract them. To investigate the short-term evolution of TE silencing, we profiled the genome-wide distribution of H3K9me3 in both human and chimpanzee induced pluripotent stem cells. We performed chromatin immunoprecipitation followed by high-throughput sequencing for H3K9me3, as well as total RNA sequencing in ten human and seven chimpanzee individuals. H3K9me3 enrichment was quantified in 141,642 regions determined to be orthologous between the two species. These H3K9me3-enriched regions were overlaid on a compiled set of 4 million orthologous TEs that can be mapped in both species.

转座子（Transposable Elements, TEs）在灵长类基因组中占比颇高。由于转座子在发育过程中可能产生有害效应，宿主会通过序列特异性KRAB型锌指蛋白（KRAB-ZNF proteins）靶向沉默转座子：这类蛋白会招募TRIM28-SETDB1复合物，以沉积抑制性组蛋白修饰H3K9me3。反之，转座子会通过获得突变逃避宿主的识别，因此KRAB型锌指蛋白需要快速演化以对抗其逃逸策略。为探究转座子沉默的短期演化规律，我们对人类与黑猩猩的诱导多能干细胞（induced pluripotent stem cells）中H3K9me3的全基因组分布特征进行了分析。我们针对H3K9me3开展了染色质免疫共沉淀结合高通量测序实验，并对10名人类个体与7只黑猩猩个体的样本进行了总RNA测序。我们在两物种间鉴定出的141,642个同源区域内对H3K9me3富集度进行了定量分析，并将这些H3K9me3富集区域与整合得到的、可在两个物种中定位的400万个同源转座子数据集进行了叠加比对。