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Chromatin-dependent regulation of secondary metabolite biosynthesis in fungi: is the picture complete?
FEMS Microbiology Reviews ( IF 10.1 ) Pub Date : 2019-11-01 , DOI: 10.1093/femsre/fuz018
Jérôme Collemare 1 , Michael F Seidl 2
Affiliation  

Fungal secondary metabolites are small molecules that exhibit diverse biological activities exploited in medicine, industry and agriculture. Their biosynthesis is governed by co-expressed genes that often co-localize in gene clusters. Most of these secondary metabolite gene clusters are inactive under laboratory conditions, which is due to a tight transcriptional regulation. Modifications of chromatin, the complex of DNA and histone proteins influencing DNA accessibility, play an important role in this regulation. However, tinkering with well-characterised chemical and genetic modifications that affect chromatin alters the expression of only few biosynthetic gene clusters, and thus the regulation of the vast majority of biosynthetic pathways remains enigmatic. In the past, attempts to activate silent gene clusters in fungi mainly focused on histone acetylation and methylation, while in other eukaryotes many other post-translational modifications are involved in transcription regulation. Thus, how chromatin regulates the expression of gene clusters remains a largely unexplored research field. In this review, we argue that focusing on only few well-characterised chromatin modifications is significantly hampering our understanding of the chromatin-based regulation of biosynthetic gene clusters. Research on underexplored chromatin modifications and on the interplay between different modifications is timely to fully explore the largely untapped reservoir of fungal secondary metabolites.

中文翻译:

真菌次级代谢物生物合成的染色质依赖性调控:图片完整吗?

真菌次级代谢产物是在医学、工业和农业中具有多种生物活性的小分子。它们的生物合成受共表达基因的控制,这些基因通常共定位于基因簇中。大多数这些次级代谢产物基因簇在实验室条件下是无活性的,这是由于严格的转录调控。染色质的修饰、影响 DNA 可及性的 DNA 和组蛋白的复合物,在该调节中起着重要作用。然而,修补影响染色质的特征明确的化学和遗传修饰只会改变少数生物合成基因簇的表达,因此绝大多数生物合成途径的调节仍然是个谜。在过去,在真菌中激活沉默基因簇的尝试主要集中在组蛋白乙酰化和甲基化上,而在其他真核生物中,许多其他翻译后修饰参与转录调控。因此,染色质如何调节基因簇的表达仍然是一个很大程度上未被探索的研究领域。在这篇综述中,我们认为仅关注少数几个特征明确的染色质修饰会严重阻碍我们对基于染色质的生物合成基因簇调控的理解。研究未充分探索的染色质修饰和不同修饰之间的相互作用是及时充分探索真菌次级代谢产物的大量未开发储库。而在其他真核生物中,许多其他翻译后修饰也参与转录调控。因此,染色质如何调节基因簇的表达仍然是一个很大程度上未被探索的研究领域。在这篇综述中,我们认为仅关注少数几个特征明确的染色质修饰会严重阻碍我们对基于染色质的生物合成基因簇调控的理解。研究未充分探索的染色质修饰和不同修饰之间的相互作用是及时充分探索真菌次级代谢产物的大量未开发储库。而在其他真核生物中,许多其他翻译后修饰也参与转录调控。因此,染色质如何调节基因簇的表达仍然是一个很大程度上未被探索的研究领域。在这篇综述中,我们认为仅关注少数几个特征明确的染色质修饰会严重阻碍我们对基于染色质的生物合成基因簇调控的理解。研究未充分探索的染色质修饰和不同修饰之间的相互作用是及时充分探索真菌次级代谢产物的大量未开发储库。我们认为,只关注少数几个特征明确的染色质修饰会严重阻碍我们对基于染色质的生物合成基因簇调控的理解。研究未充分探索的染色质修饰和不同修饰之间的相互作用是及时充分探索真菌次级代谢产物的大量未开发储库。我们认为,只关注少数几个特征明确的染色质修饰会严重阻碍我们对基于染色质的生物合成基因簇调控的理解。研究未充分探索的染色质修饰和不同修饰之间的相互作用是及时充分探索真菌次级代谢产物的大量未开发储库。
更新日期:2020-02-10
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