Secombe Julie, Eisenman Robert N
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Cell Cycle. 2007 Jun 1;6(11):1324-8. doi: 10.4161/cc.6.11.4269. Epub 2007 Jun 14.
Epigenetic regulation of transcription refers to reversible, heritable changes in gene expression that occur in the absence of changes in DNA sequence. A major epigenetic mechanism involves the covalent modification of nucleosomal histones to create binding sites for transcriptional regulators and chromatin remodeling complexes that mediate activation or repression of transcription. While it has been known for a number of years that many histone modifications are reversible, it has only recently been shown that methyl groups are enzymatically removed from lysine residues. Here we discuss the recent characterization of a new class of demethylase enzyme, the JARID1 family, which catalyzes the removal of methyl groups from lysine 4 of histone H3. We summarize recent findings regarding the function of this family of proteins, focusing on our characterization of Little imaginal discs (Lid), the sole JARID1 family protein in Drosophila, which is rate-limiting for Myc-induced cell growth. Finally, we propose models to explain the role of Lid in Myc-mediated growth and discuss the relevance of these findings to human disease and tumor formation.
转录的表观遗传调控是指在DNA序列没有变化的情况下发生的基因表达的可逆、可遗传变化。一种主要的表观遗传机制涉及核小体组蛋白的共价修饰，以创建转录调节因子和染色质重塑复合物的结合位点，这些复合物介导转录的激活或抑制。虽然多年来人们已经知道许多组蛋白修饰是可逆的，但直到最近才表明甲基基团可以通过酶促作用从赖氨酸残基上去除。在这里，我们讨论一类新的去甲基化酶——JARID1家族的最新特征，该家族催化从组蛋白H3的赖氨酸4上去除甲基基团。我们总结了关于该蛋白家族功能的最新发现，重点是我们对果蝇中唯一的JARID1家族蛋白小成虫盘（Lid）的表征，它是Myc诱导细胞生长的限速因子。最后，我们提出模型来解释Lid在Myc介导的生长中的作用，并讨论这些发现与人类疾病和肿瘤形成的相关性。
