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Integrative analyses shed new light on human ribosomal protein gene regulation.

ABSTRACT: Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals.

SUBMITTER: Li X

PROVIDER: S-EPMC4921865 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other

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Integrative analyses shed new light on human ribosomal protein gene regulation.

Li Xin X Zheng Yiyu Y Hu Haiyan H Li Xiaoman X

Scientific reports 20160627

Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 exper ...[more]

PMID: 27346035

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Project description:Fungi dominate the recycling of carbon sequestered in woody biomass. This process of organic turnover was first evolved among "white rot" fungi that degrade lignin to access carbohydrates and later evolved multiple times toward more efficient strategies to selectively target carbohydrates-"brown rot." The brown rot adaption was often explained by mechanisms to deploy reactive oxygen species (ROS) to oxidatively attack wood structures. However, its genetic basis remains unclear, especially in the context of gene contractions of conventional carbohydrate-active enzymes (CAZYs) relative to white rot ancestors. Here, we hypothesized that these apparent gains in brown rot efficiency despite gene losses were due, in part, to upregulation of the retained genes. We applied comparative transcriptomics to multiple species of both rot types grown across a wood wafer to create a gradient of progressive decay and to enable tracking temporal gene expression. Dozens of "decay-stage-dependent" ortho-genes were isolated, narrowing a pool of candidate genes with time-dependent regulation unique to brown rot fungi. A broad comparison of the expression timing of CAZY families indicated a temporal regulatory shift of lignocellulose-oxidizing genes toward early stages in brown rot compared to white rot, enabling the segregation of oxidative treatment ahead of hydrolysis. These key brown rot ROS-generating genes with iron ion binding functions were isolated. Moreover, transcription energy was shifted to be invested on the retained GHs in brown rot fungi to strengthen carbohydrate conversion. Collectively, these results support the hypothesis that gene regulation shifts played a pivotal role in brown rot adaptation.IMPORTANCE Fungi dominate the turnover of wood, Earth's largest pool of aboveground terrestrial carbon. Fungi first evolved this capacity by degrading lignin to access and hydrolyze embedded carbohydrates (white rot). Multiple lineages, however, adapted faster reactive oxygen species (ROS) pretreatments to loosen lignocellulose and selectively extract sugars (brown rot). This brown rot "shortcut" often coincided with losses (>60%) of conventional lignocellulolytic genes, implying that ROS adaptations supplanted conventional pathways. We used comparative transcriptomics to further pursue brown rot adaptations, which illuminated the clear temporal expression shift of ROS genes, as well as the shift toward synthesizing more GHs in brown rot relative to white rot. These imply that gene regulatory shifts, not simply ROS innovations, were key to brown rot fungal evolution. These results not only reveal an important biological shift among these unique fungi, but they may also illuminate a trait that restricts brown rot fungi to certain ecological niches.

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Integrative analyses shed new light on human ribosomal protein gene regulation.

Publications

Integrative analyses shed new light on human ribosomal protein gene regulation.

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