Dynamic control of the T-cell specification gene regulatory network.
Dynamic control of the T-cell specification gene regulatory network.
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DOI：
10.1016/j.coisb.2019.10.012
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发表时间：
2019-12
影响因子：
3.7
通讯作者：
E. Rothenberg
中科院分区：
文献类型：
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作者：
E. Rothenberg
在出生后小鼠中，多能血液前体细胞成为定型T细胞前体的规范涉及几个相互作用但功能不同的模块的基因调控网络。这个网络的许多环节已被确定的扰动测试和功能基因组学。然而，使用网络模型来预测现实生活中的承诺过程的动力学仍然是困难的，部分原因是抑制性染色质状态的坚韧性，以及转录因子通过竞争性招募到替代位点（“辅调节因子盗窃”）来影响彼此的结合位点选择的能力。为了预测动力学，未来的模型将需要纳入有关染色质状态变化动力学和更复杂的理解的蛋白质组学和转录因子复合物的合作DNA位点选择的机械信息。
Specification of multipotent blood precursor cells in postnatal mice to become committed T-cell precursors involves a gene regulatory network of several interacting but functionally distinct modules. Many links of this network have been defined by perturbation tests and by functional genomics. However, using the network model to predict real-life kinetics of the commitment process is still difficult, partly due to the tenacity of repressive chromatin states, and to the ability of transcription factors to affect each other’s binding site choices through competitive recruitment to alternative sites (“coregulator theft”). To predict kinetics, future models will need to incorporate mechanistic information about chromatin state change dynamics and more sophisticated understanding of the proteomics and cooperative DNA site choices of transcription factor complexes.