Gahan James M, Helfrich Lily W, Wetzel Laura A, Bhanu Natarajan V, Yuan Zuo-Fei, Garcia Benjamin A, Klose Rob, Booth David S
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Biochemistry, University of Oxford, Oxford, UK.
bioRxiv. 2024 May 30:2024.05.28.596151. doi: 10.1101/2024.05.28.596151.
Gene expression is tightly controlled during animal development to allow the formation of specialized cell types. Our understanding of how animals evolved this exquisite regulatory control remains elusive, but evidence suggests that changes in chromatin-based mechanisms may have contributed. To investigate this possibility, here we examine chromatin-based gene regulatory features in the closest relatives of animals, choanoflagellates. Using as a model system, we examined chromatin accessibility and histone modifications at the genome scale and compared these features to gene expression. We first observed that accessible regions of chromatin are primarily associated with gene promoters and found no evidence of distal gene regulatory elements resembling the enhancers that animals deploy to regulate developmental gene expression. Remarkably, a histone modification deposited by polycomb repressive complex 2, histone H3 lysine 27 trimethylation (H3K27me3), appeared to function similarly in to its role in animals, because this modification decorated genes with cell type-specific expression. Additionally, H3K27me3 marked transposons, retaining what appears to be an ancestral role in regulating these elements. We further uncovered a putative new bivalent chromatin state at cell type-specific genes that consists of H3K27me3 and histone H3 lysine 4 mono-methylation (H3K4me1). Together, our discoveries support the scenario that gene-associated histone modification states that underpin development emerged before the evolution of animal multicellularity.
在动物发育过程中，基因表达受到严格控制，以允许形成特化的细胞类型。我们对动物如何进化出这种精细的调控控制的理解仍然难以捉摸，但有证据表明基于染色质的机制变化可能起到了作用。为了研究这种可能性，我们在此研究了动物的近亲领鞭毛虫中基于染色质的基因调控特征。以领鞭毛虫作为模型系统，我们在全基因组范围内检测了染色质可及性和组蛋白修饰，并将这些特征与基因表达进行了比较。我们首先观察到，染色质的可及区域主要与基因启动子相关，并且没有发现类似于动物用于调控发育基因表达的增强子的远端基因调控元件的证据。值得注意的是，由多梳抑制复合物2沉积的组蛋白修饰——组蛋白H3赖氨酸27三甲基化（H3K27me3），在领鞭毛虫中的功能似乎与其在动物中的作用相似，因为这种修饰标记了具有细胞类型特异性表达的基因。此外，H3K27me3标记了转座子，保留了其在调控这些元件方面似乎是祖先的作用。我们进一步在细胞类型特异性基因上发现了一种推定的新的二价染色质状态，它由H3K27me3和组蛋白H3赖氨酸4单甲基化（H3K4me1）组成。总之，我们的发现支持了这样一种情况：在动物多细胞性进化之前，支撑发育的与基因相关的组蛋白修饰状态就已经出现。
