近期Biochemical Journal發表了「發育與疾病相關基因」教育部重點實驗室」萬亞坤課題組的研究工作 (Role of the repressor Oaf3p in the recruitment of transcription factors and chromatin dynamics during oleate response, 2012 Oct 23)。
細胞通過多種調控機制對外界刺激做出反應。各種調控機制之間的相互作用是細胞適應外界環境的關鍵所在。本論文系統地研究了轉錄因子和染色質調控因子之間如何共同調控對脂肪酸誘導產生的反應。參與脂肪酸B-氧化作用的基因受4個轉錄因子Oaf1, Pip2, Oaf3和Adr1的調控。此外組蛋白變體Htz1也參與了脂肪酸B-氧化以及過氧化物酶體的形成。通過染色質免疫沉澱技術，我們發現組蛋白變體Htz1調控著轉錄抑制子Oaf3在啟動子區域的結合。同時Adr1對Htz1在啟動子部位的結合也扮演著重要的角色。更為有趣的是，我們首次發現，轉錄調控因子Oaf3像染色質調控蛋白一樣，對脂肪酸應答DNA分子的染色質結構有明顯的調控作用。該課題得到了國家自然基金委（31071146， 31271365）以及東南大學「發育與疾病相關基因」教育部重點實驗室開放課題的支持。（生物谷Bioon.com）
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.