Center for Genomic Regulation, Barcelona Institute for Science and Technology and Universitat Pompeu Fabra, Barcelona, Spain.
Trends Cell Biol. 2021 Oct;31(10):792-800. doi: 10.1016/j.tcb.2021.04.001. Epub 2021 May 17.
Histone methylation is required for the establishment and maintenance of gene expression patterns that determine cellular identity, and its perturbation often leads to aberrant development and disease. Recruitment of histone methyltransferases (HMTs) to gene regulatory elements (GREs) of developmental genes is important for the correct activation and silencing of these genes, but the drivers of this recruitment are largely unknown. Here we propose that lineage-instructive transcription factors (Lin-TFs) act as general recruiters of HMT complexes to cell type-specific GREs through protein-protein interactions. We also postulate that the specificity of these interactions is dictated by Lin-TF post-translational modifications (PTMs), which act as a 'transcription factor code' that can determine the directionality of cell fate decisions during differentiation and development.
组蛋白甲基化对于建立和维持决定细胞身份的基因表达模式是必需的,其扰动常常导致异常发育和疾病。组蛋白甲基转移酶(HMTs)募集到发育基因的基因调控元件(GREs)对于这些基因的正确激活和沉默非常重要,但这种募集的驱动因素在很大程度上是未知的。在这里,我们提出谱系指令性转录因子(Lin-TFs)通过蛋白-蛋白相互作用作为 HMT 复合物到细胞类型特异性 GREs 的一般招募者。我们还假设这些相互作用的特异性由 Lin-TF 翻译后修饰(PTMs)决定,这些修饰作为“转录因子密码”,可以在分化和发育过程中决定细胞命运决定的方向性。