MLL in maintenance and regulation of HOX gene expression

MLL最初被发现是因为它参与了染色体易位， 会导致白血病。MLL是维持靶基因正确表达所必需的 基因，包括一些聚集的HOX基因。有越来越多的证据表明MLL 通过调节染色质结构来调节基因的表达 蛋白质结构域，以及它招募的额外蛋白质。我们的数据 证明MLL保护Hoxa9靶基因中的特定CpG DNA序列 来自甲基化的基因座，从而允许基因表达，规范的Hoxa9和 一种微小的RNA前体。因此，我们提出了一种新的MLL函数模型。我们 提出MLL通过阻止CpG来维持其靶基因表达的潜能 发育过程中的岛甲基化。MLL保护不受CpG甲基化的影响 在随后的细胞分裂中，基因的表达是“开放的”和允许的。 该标记不易改变，因此可以起到保持记忆的作用 先前的基因表达。我们将确定MLL在DNA保护中的作用 甲基化，MLL CpG DNA结合CXXC结构域对MLL融合的特定作用 功能，以及一种特定的microRNA对MLL白血病的发生。

MLL was first identified because it is involved in chromosomal translocations that result in leukemia. MLL is required for maintaining the proper expression of target genes, including some of the clustered HOX genes. There is growing evidence that MLL regulates gene expression by modulating chromatin structure via activity of some of its protein domains as well as through additional proteins that it recruits. Our data demonstrate that MLL protects specific CpG DNA sequences in the Hoxa9 target gene locus from methylation, thereby allowing gene expression, both of canonical Hoxa9 and of a microRNA precursor. We therefore propose a novel model of MLL function. We propose that MLL maintains the potential to express its target genes by preventing CpG island methylation during development. MLL protection from CpG methylation keeps the locus "open" and permissive for gene expression through subsequent cell divisions. This mark is not easily changed and, therefore, can function to maintain memory of previous gene expression. We will determine the role of MLL in protection from DNA methylation, the specific role of the MLL CpG DNA binding CXXC domain to MLL fusion function, and of a specific microRNA to MLL leukemogenesis.