Rice K L, Hormaeche I, Licht J D
Division of Hematology/Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Oncogene. 2007 Oct 15;26(47):6697-714. doi: 10.1038/sj.onc.1210755.
The molecular processes governing hematopoiesis involve the interplay between lineage-specific transcription factors and a series of epigenetic tags, including DNA methylation and covalent histone tail modifications, such as acetylation, methylation, phosphorylation, SUMOylation and ubiquitylation. These post-translational modifications, which collectively constitute the 'histone code', are capable of affecting chromatin structure and gene transcription and are catalysed by opposing families of enzymes, allowing the developmental potential of hematopoietic stem cells to be dynamically regulated. The essential role of these enzymes in regulating normal blood development is highlighted by the finding that members from all families of chromatin regulators are targets for dysregulation in many hematological malignancies, and that patterns of histone modification are globally affected in cancer as well as the regulatory regions of specific oncogenes and tumor suppressors. The discovery that these epigenetic marks can be reversed by compounds targeting aberrant transcription factor/co-activator/co-repressor interactions and histone-modifying activities, provides the basis for an exciting field in which the epigenome of cancer cells may be manipulated with potential therapeutic benefits.
调控造血作用的分子过程涉及谱系特异性转录因子与一系列表观遗传标记之间的相互作用，这些表观遗传标记包括DNA甲基化和共价组蛋白尾部修饰，如乙酰化、甲基化、磷酸化、SUMO化和泛素化。这些翻译后修饰共同构成了“组蛋白密码”，能够影响染色质结构和基因转录，并由相对的酶家族催化，从而使造血干细胞的发育潜能得到动态调控。染色质调节因子所有家族的成员都是许多血液系统恶性肿瘤中失调的靶点，并且癌症以及特定癌基因和肿瘤抑制基因的调控区域中的组蛋白修饰模式也受到全局影响，这一发现突出了这些酶在调节正常血液发育中的重要作用。靶向异常转录因子/共激活因子/共抑制因子相互作用和组蛋白修饰活性的化合物可以逆转这些表观遗传标记，这一发现为一个令人兴奋的领域奠定了基础，在这个领域中，癌细胞的表观基因组可能被操纵并具有潜在的治疗益处。
