Psychology Department, 1202 West Johnson Street, University of Wisconsin-Madison, Madison, WI 53706, USA.
Psychoneuroendocrinology. 2009 Dec;34 Suppl 1(Suppl 1):S39-47. doi: 10.1016/j.psyneuen.2009.05.012.
The differential exposure to circulating steroid hormones during brain development can have lasting consequences on brain function and behavior; therefore, the tight control of steroid hormone action within the developing brain is necessary for the expression of appropriate sex-typical behavior patterns later in life. The restricted control of steroid hormone action at the level of the DNA can be accomplished through the recruitment of coregulatory complexes. Nuclear receptor action can either be enhanced by the recruitment of coactivator complexes or suppressed by the formation of corepressor complexes. Alternatively, the regulation of nuclear receptor-mediated gene transcription in the developing brain may involve a dynamic process of coactivator and corepressor function on DNA. It is likely that understanding how different combinations of coregulatory matrixes assembly on DNA will lead to further understanding of heterogeneous responses to nuclear receptor activation. We will discuss how coregulators influence gene transcription and repression, the role of chromatin-binding factors in the regulation of gene transcription, and their potential impact on brain development.
在大脑发育过程中,循环类固醇激素的差异暴露可能对大脑功能和行为产生持久的影响;因此,为了在以后的生活中表现出适当的性别典型行为模式,需要严格控制类固醇激素在发育中的大脑中的作用。在 DNA 水平上对类固醇激素作用的限制控制可以通过募集共调节复合物来完成。核受体的作用可以通过募集共激活复合物来增强,也可以通过形成共抑制复合物来抑制。或者,发育中大脑中核受体介导的基因转录的调节可能涉及 DNA 上共激活剂和共抑制剂功能的动态过程。了解不同的共调节基质组合如何在 DNA 上组装,可能会进一步了解对核受体激活的异质反应。我们将讨论共调节剂如何影响基因转录和抑制,染色质结合因子在基因转录调节中的作用,以及它们对大脑发育的潜在影响。