Ikaros fingers on lymphocyte differentiation.
Ikaros fingers on lymphocyte differentiation.
复制标题
DOI：
10.1007/s12185-014-1644-5
复制
发表时间：
2014-09
影响因子：
2.1
通讯作者：
Georgopoulos, Katia
中科院分区：
文献类型：
--
作者：
Yoshida, Toshimi;Georgopoulos, Katia
DNA 结合蛋白 Ikaros 家族是淋巴细胞分化的关键调节因子。在多能造血祖细胞中，Ikaros 支持促进淋巴细胞分化的基因的转录启动。 Ikaros 将核小体重塑脱乙酰酶复合物 (NuRD) 靶向淋巴谱系基因，从而增加染色质可及性和转录启动。淋巴谱系特化后，Ikaros 表达升高至中间 B 细胞和 T 细胞前体的特征水平，这是支持成熟和预防白血病发生所必需的。 T 细胞前体中 Ikaros 的缺失使得 NuRD 复合物能够抑制淋巴细胞基因，并将其靶向范围扩展到支持生长和增殖的基因，从而导致它们激活并引发一系列导致白血病发生的事件。 B 细胞前体细胞中 Ikaros 的缺失会阻碍分化，并通过增强整合素信号传导来维持基质粘附。 Ikaros 缺陷的前 B 细胞中整合素和细胞因子信号传导的结合可促进其生存和自我更新。高度依赖于 Ikaros 的淋巴细胞分化阶段通过 Ikaros 转录的变化得到强调，并得到汇聚于 Ikzf1 基因座的阶段特异性调控网络的复杂网络的支持。越来越明显的是，了解 Ikaros 上游和下游的调控网络不仅对于我们了解正常的淋巴细胞生成至关重要，而且对于确定支持小鼠和人类造血系统恶性肿瘤的机制也至关重要。
The Ikaros family of DNA binding proteins are critical regulators of lymphocyte differentiation. In multipotent hematopoietic progenitors, Ikaros supports transcriptional priming of genes promoting lymphocyte differentiation. Ikaros targets the Nucleosome Remodeling Deacetylase complex (NuRD) to lymphoid lineage genes, thereby increasing chromatin accessibility and transcriptional priming. After lymphoid lineage specification, Ikaros expression is raised to levels characteristic of intermediate B cell and T cell precursors, which is necessary to support maturation and prevent leukemogenesis. Loss of Ikaros in T cell precursors allows the NuRD complex to repress lymphocyte genes and extends its targeting to genes that support growth and proliferation, causing their activation and triggering a cascade of events that leads to leukemogenesis. Loss of Ikaros in B cell precursors blocks differentiation and perpetuates stromal adhesion by enhancing integrin signaling. The combination of integrin and cytokine signaling in Ikaros-deficient pre-B cells promotes their survival and self-renewal. The stages of lymphocyte differentiation that are highly dependent on Ikaros are underscored by changes in Ikaros transcription, supported by a complex network of stage-specific regulatory networks that converge upon the Ikzf1 locus. It is increasingly apparent that understanding the regulatory networks that operate upstream and downstream of Ikaros is critical not only for our understanding of normal lymphopoiesis, but also in placing the right finger on the mechanisms that support hematopoietic malignancies in mouse and human.
登录
查看更多内容
E2A蛋白促进淋巴酸化的多能祖细胞的发展。
影响因子：
32.4
作者：
Dias, Sheila;Mansson, Robert;Gurbuxani, Sandeep;Sigvardsson, Mikael;Kee, Barbara L.
通讯作者：
Kee, Barbara L.
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Igarashi, H;Gregory, SC;Kincade, PW
通讯作者：
Kincade, PW
影响因子：
64.5
作者：
Adolfsson, J;Månsson, R;Jacobsen, SEW
通讯作者：
Jacobsen, SEW
影响因子：
50.3
作者：
Goardon, Nicolas;Marchi, Emanuele;Vyas, Paresh
通讯作者：
Vyas, Paresh