Short-Circuiting Gene Regulatory Networks: Origins of B Cell Lymphoma.
Short-Circuiting Gene Regulatory Networks: Origins of B Cell Lymphoma.
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短路基因调控网络：B 细胞淋巴瘤的起源。
DOI：
10.1016/j.tig.2015.09.006
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Payton,JacquelineE
中科院分区：
文献类型：
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作者：
Koues,OliviaI;Oltz,EugeneM;Payton,JacquelineE
B细胞淋巴瘤（bcl）的特点是与正常B细胞相比，基因表达普遍失调。最近的表观基因组学研究确定了在BCL中改变活性的调控元件（REs），以驱动这些致病性表达的一些变化。在转化过程中，多种机制被用来改变RE的活性，包括染色质修饰剂功能的扰动，这可能导致B细胞表观基因组的修改。遗传和体细胞变异也通过破坏转录因子（TF）结合来改变RE功能。非编码rna （ncRNAs）的异常表达通过直接抑制和转录后靶向调控参与B细胞分化的基因。这些发现已经建立了B细胞转化的表观遗传病因学，正在开发新的治疗方法。
B cell lymphomas (BCLs) are characterized by widespread deregulation of gene expression compared with their normal B cell counterparts. Recent epigenomic studies definedcis-regulatory elements (REs) whose activities are altered in BCL to drive some of these pathogenic expression changes. During transformation, multiple mechanisms are employed to alter RE activities, including perturbations in the function of chromatin modifiers, which can lead to revision of the B cell epigenome. Inherited and somatic variants also alter RE function via disruption of transcription factor (TF) binding. Aberrant expression of noncoding RNAs (ncRNAs) deregulates genes involved in B cell differentiation via direct repression and post-transcriptional targeting. These discoveries have established epigenetic etiologies for B cell transformation that are being exploited in novel therapeutic approaches.