近期Biochemical Journal发表了“发育与疾病相关基因”教育部重点实验室”万亚坤课题组的研究工作 (Role of the repressor Oaf3p in the recruitment of transcription factors and chromatin dynamics during oleate response, 2012 Oct 23)。
细胞通过多种调控机制对外界刺激做出反应。各种调控机制之间的相互作用是细胞适应外界环境的关键所在。本论文系统地研究了转录因子和染色质调控因子之间如何共同调控对脂肪酸诱导产生的反应。参与脂肪酸B-氧化作用的基因受4个转录因子Oaf1, Pip2, Oaf3和Adr1的调控。此外组蛋白变体Htz1也参与了脂肪酸B-氧化以及过氧化物酶体的形成。通过染色质免疫沉淀技术，我们发现组蛋白变体Htz1调控着转录抑制子Oaf3在启动子区域的结合。同时Adr1对Htz1在启动子部位的结合也扮演着重要的角色。更为有趣的是，我们首次发现，转录调控因子Oaf3像染色质调控蛋白一样，对脂肪酸应答DNA分子的染色质结构有明显的调控作用。该课题得到了国家自然基金委（31071146， 31271365）以及东南大学“发育与疾病相关基因”教育部重点实验室开放课题的支持。（生物谷Bioon.com）
doi:10.1042/BJ20121029
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Role of the repressor Oaf3p in the recruitment of transcription factors and chromatin dynamics during oleate response
Wan Y, Arens CE, Wang S, Zuo X, Zhuo Y, Xing J.
Cellular responses to environmental stimuli are mediated by the coordinate activity of multiple control mechanisms, which result in dynamics of cell function. Communication between different levels of regulation is central for this adaptability. This study focuses on the interplay between transcriptional regulators and chromatin modifiers to cooperatively regulate transcription in response to a fatty acid stimulus. Genes involved in β-oxidation of fatty acids are highly induced in response to fatty acid exposure by four gene specific transcriptional regulators, Oaf1p, Pip2p, Oaf3p and Adr1p. Here, we examine the interplay of these factors with histone variant H2A.Z (Htz1p) in regulating the POT1 gene encoding peroxisomal thiolase, and PIP2 genes encoding the autoregulatory oleate specific transcriptional activator. Temporal resolution of ChIP data indicates that Htz1p is required for the timely removal of the transcriptional repressor Oaf3p during oleate induction. Adr1p plays an important role in the assembly of Htz1p-containing nucleosomes on the POT1 and PIP2 promoters. We also investigated the function of the uncharacterized transcriptional inhibitor, Oaf3p. Deletion of OAF3 led to faster POT1 mRNA accumulation than in the wild-type. Most impressively, a highly protected nucleosome structure on the POT1 promoter during activation was observed in the OAF3 mutant cells in response to oleate induction.
