Genome-wide analysis of combinatorial cis-regulatory control of early blood progenitor cells

血液干细胞为一个人的一生提供源源不断的新血细胞--S。它们的转录调控，即微调哪些基因在任何给定的时间都应该是活跃的，对它们的正常功能至关重要。此外，当基因活动的这种微妙平衡被破坏时，会出现大量的白血病。然而，人们对决定适当基因活性的分子机制知之甚少，尽管很明显，它们必须由转录因子网络控制。转录因子是负责控制其他基因活性的基因。这项提议旨在发现正常血液干细胞的关键调控者如何整合到更广泛的血液干细胞调控网络中。这将为未来的研究奠定基础，这些研究旨在确定特定基因的扰动是如何导致白血病的。

Blood stem cells provide the constant supply of new blood cells throughout a person?s lifetime. Their transcriptional regulation, i.e. the fine tuning of which genes should be active at any given time, is critical for their normal function. Moreover, a large number of leukaemias arise, when this fine balance of gene activities is disturbed. However, very little is known about the molecular mechanisms responsible for setting appropriate gene activities although it is clear that they must be controlled by networks of transcription factors. Transcription factors are genes responsible for controlling the activity of other genes. This proposal aims to discover how key regulators of normal blood stem cells are integrated into the wider blood stem cell regulatory networks. This will lay the foundation for future studies aiming to identify how perturbation of specific genes causes leukaemia.