Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Semin Immunol. 2010 Dec;22(6):313-22. doi: 10.1016/j.smim.2010.07.001. Epub 2010 Sep 15.
Many aspects of gene function are coordinated by changes in the epigenome, which include dynamic revisions of chromatin modifications, genome packaging, subnuclear localization, and chromosome conformation. All of these mechanisms are used by developing lymphocytes to regulate the assembly of functional antigen receptor genes by V(D)J recombination. This somatic rearrangement of the genome must be tightly regulated to ensure proper B and T cell development and to avoid chromosomal translocations that cause lymphoid tumors. V(D)J recombination is controlled by a complex interplay between cis-acting regulatory elements that use transcription factors as liaisons to communicate with epigenetic pathways. Genetic-epigenetic crosstalk is a key strategy employed by precursor lymphocytes to modulate chromatin configurations at Ig and Tcr loci and thereby permit or deny access to a single V(D)J recombinase complex. This article describes our current knowledge of how genetic elements orchestrate crosstalk with epigenetic mechanisms to regulate recombinase accessibility via localized, regional, or long-range changes in chromatin.
基因功能的许多方面都受到表观基因组变化的协调，这些变化包括染色质修饰、基因组包装、亚核定位和染色体构象的动态修正。所有这些机制都被发育中的淋巴细胞用来调节功能性抗原受体基因通过 V(D)J 重组的组装。这种基因组的体细胞重排必须受到严格的调控，以确保 B 和 T 细胞的正常发育，并避免导致淋巴肿瘤的染色体易位。V(D)J 重组受到顺式作用调节元件之间的复杂相互作用的控制，这些调节元件利用转录因子作为联络人，与表观遗传途径进行通信。遗传-表观遗传的串扰是前体细胞淋巴细胞用来调节 Ig 和 TCR 基因座染色质构型的一种关键策略，从而允许或拒绝单个 V(D)J 重组酶复合物的进入。本文描述了我们目前对遗传元件如何通过局部、区域或长距离的染色质变化与表观遗传机制进行串扰来调节重组酶可及性的认识。
