Sze Christie C, Shilatifard Ali
Department of Biochemistry and Molecular Genetics and Robert H. Lurie NCI Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611.
Cold Spring Harb Perspect Med. 2016 Nov 1;6(11):a026427. doi: 10.1101/cshperspect.a026427.
During development, precise spatiotemporal patterns of gene expression are coordinately controlled by cis-regulatory modules known as enhancers. Their crucial role in development helped spur numerous studies aiming to elucidate the functional properties of enhancers within their physiological and disease contexts. In recent years, the role of enhancer malfunction in tissue-specific tumorigenesis is increasingly investigated. Here, we direct our focus to two primary players in enhancer regulation and their role in cancer pathogenesis: MLL3 and MLL4, members of the COMPASS family of histone H3 lysine 4 (H3K4) methyltransferases, and their complex-specific subunit UTX, a histone H3 lysine 27 (H3K27) demethylase. We review the most recent evidence on the underlying roles of MLL3/MLL4 and UTX in cancer and highlight key outstanding questions to help drive future research and contribute to our fundamental understanding of cancer and facilitate identification of therapeutic opportunities.
在发育过程中，基因表达的精确时空模式由被称为增强子的顺式调控模块协调控制。它们在发育中的关键作用促使众多研究旨在阐明增强子在其生理和疾病背景下的功能特性。近年来，增强子功能异常在组织特异性肿瘤发生中的作用受到越来越多的研究。在这里，我们将重点关注增强子调控中的两个主要参与者及其在癌症发病机制中的作用：MLL3和MLL4，组蛋白H3赖氨酸4（H3K4）甲基转移酶COMPASS家族的成员，以及它们复合物特异性亚基UTX，一种组蛋白H3赖氨酸27（H3K27）去甲基化酶。我们综述了关于MLL3/MLL4和UTX在癌症中潜在作用的最新证据，并强调了关键的悬而未决的问题，以帮助推动未来的研究，并有助于我们对癌症的基本理解，促进治疗机会的识别。
