Becker Justin S, Nicetto Dario, Zaret Kenneth S
Institute for Regenerative Medicine, Epigenetics Program, and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Institute for Regenerative Medicine, Epigenetics Program, and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Smilow Center for Translational Research, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA.
Trends Genet. 2016 Jan;32(1):29-41. doi: 10.1016/j.tig.2015.11.001. Epub 2015 Dec 8.
Establishing and maintaining cell identity depends on the proper regulation of gene expression, as specified by transcription factors and reinforced by epigenetic mechanisms. Among the epigenetic mechanisms, heterochromatin formation is crucial for the preservation of genome stability and the cell type-specific silencing of genes. The heterochromatin-associated histone mark H3K9me3, although traditionally associated with the noncoding portions of the genome, has emerged as a key player in repressing lineage-inappropriate genes and shielding them from activation by transcription factors. Here we describe the role of H3K9me3 heterochromatin in impeding the reprogramming of cell identity and the mechanisms by which H3K9me3 is reorganized during development and cell fate determination.
建立和维持细胞身份取决于基因表达的适当调控，转录因子对此进行了明确规定，并由表观遗传机制加以强化。在表观遗传机制中，异染色质的形成对于维持基因组稳定性以及基因的细胞类型特异性沉默至关重要。异染色质相关的组蛋白标记H3K9me3，尽管传统上与基因组的非编码部分相关，但已成为抑制谱系不适当基因并使其免受转录因子激活的关键因素。在这里，我们描述了H3K9me3异染色质在阻碍细胞身份重编程中的作用，以及在发育和细胞命运决定过程中H3K9me3重组的机制。
