Effects of MBTD1 on gene expression

The NuA4/TIP60 acetyltransferase complex is a key regulator of genome expression and stability. Here, we identified MBTD1 as a new stable subunit of the complex and gleaned intriguing insights into TIP60’s function. Harboring a histone reader domain for H4K20me1/2, MBTD1 allows TIP60 to associate with specific gene promoters and to promote the repair of DNA double strand breaks by homologous recombination. Total RNA was analyzed on Illumina Human HT-12 V4.0 expression beadchip by McGill University and Genome Québec innovation Centre CRISPR/Cas9 technology was used to produce MBTD1 knockout cells in U2OS and to perform genome-wide expression analysis on three different clones compared to wild type cells.

NuA4/TIP60乙酰转移酶复合物（NuA4/TIP60 acetyltransferase complex）是调控基因组表达与稳定性的关键因子。本研究鉴定出MBTD1为该复合物的新型稳定亚基，并获得了关于TIP60功能的多项引人关注的新见解。MBTD1携带有识别H4K20me1/2的组蛋白阅读器结构域，可介导TIP60结合特定基因启动子，并促进同源重组通路修复DNA双链断裂（DNA double strand breaks）。实验方面，麦吉尔大学与魁北克基因组创新中心使用Illumina Human HT-12 V4.0表达微珠芯片（Illumina Human HT-12 V4.0 expression beadchip）完成了总RNA的表达分析；本研究同时采用CRISPR/Cas9技术（CRISPR/Cas9 technology）在U2OS细胞中构建MBTD1基因敲除细胞系，并针对3株独立敲除克隆与野生型细胞开展全基因组表达谱分析。