Interdisciplinary Center for Bioinformatics, University Leipzig, Leipzig, Germany.
Bioessays. 2012 Oct;34(10):841-8. doi: 10.1002/bies.201100190. Epub 2012 Jul 23.
Epigenetic control of gene expression by chromatin remodeling is critical for adult stem cell function. A decline in stem cell function is observed during aging, which is accompanied by changes in the chromatin structure that are currently unexplained. Here, we hypothesize that these epigenetic changes originate from the limited cellular capability to inherit epigenetic information. We suggest that spontaneous loss of histone modification, due to fluctuations over short time scales, gives rise to long-term changes in DNA methylation and, accordingly, in gene expression. These changes are assumed to impair stem cell function and, thus, to contribute to aging. We discuss cell replication as a major source of fluctuations in histone modification patterns. Gene silencing by our proposed mechanism can be interpreted as a manifestation of the conflict between the stem cell plasticity required for tissue regeneration and the permanent silencing of potentially deleterious genomic sequences.
染色质重塑对基因表达的表观遗传控制对成体干细胞功能至关重要。在衰老过程中观察到干细胞功能下降，同时伴随着目前尚无法解释的染色质结构变化。在这里，我们假设这些表观遗传变化源于细胞继承表观遗传信息的能力有限。我们认为，由于短时间尺度上的波动，组蛋白修饰的自发丧失会导致 DNA 甲基化的长期变化，并相应地导致基因表达的变化。这些变化被认为会损害干细胞功能，从而导致衰老。我们讨论了细胞复制作为组蛋白修饰模式波动的主要来源。我们提出的机制通过基因沉默可以被解释为组织再生所需的干细胞可塑性与潜在有害基因组序列的永久沉默之间的冲突的表现。
