Journal of Genetics and Genomics

Integration of lipidomics and metabolomics for in-depth understanding of cellular mechanism and disease progression

Raoxu Wang, Bowen Li, Sin Man Lam, Guanghou Shui

2020, 47(2): 69-83. doi: 10.1016/j.jgg.2019.11.009

Abstract (161) HTML PDF (2)

Abstract:
Mass spectrometry (MS)-based omics technologies are now widely used to profile small molecules in multiple matrices to confer comprehensive snapshots of cellular metabolic phenotypes. The metabolomes of cells, tissues, and organisms comprise a variety of molecules including lipids, amino acids, sugars, organic acids, and so on. Metabolomics mainly focus on the hydrophilic classes, while lipidomics has emerged as an independent omics owing to the complexities of the organismal lipidomes. The potential roles of lipids and small metabolites in disease pathogenesis have been widely investigated in various human diseases, but system-level understanding is largely lacking, which could be partly attributed to the insufficiency in terms of metabolite coverage and quantitation accuracy in current analytical technologies. While scientists are continuously striving to develop high-coverage omics approaches, integration of metabolomics and lipidomics is becoming an emerging approach to mechanistic investigation. Integration of metabolome and lipidome offers a complete atlas of the metabolic landscape, enabling comprehensive network analysis to identify critical metabolic drivers in disease pathology, facilitating the study of interconnection between lipids and other metabolites in disease progression. In this review, we summarize omics-based findings on the roles of lipids and metabolites in the pathogenesis of selected major diseases threatening public health. We also discuss the advantages of integrating lipidomics and metabolomics for in-depth understanding of molecular mechanism in disease pathogenesis.

Defining endogenous barcoding sites for CRISPR/Cas9-based cell lineage tracing in zebrafish

Chang Ye, Zhuoxin Chen, Zhan Liu, Feng Wang, Xionglei He

2020, 47(2): 85-91. doi: 10.1016/j.jgg.2019.11.012

Abstract (68) HTML PDF (1)

Abstract:
There is a growing interest in developing experimental methods for tracking the developmental cell lineages of a complex organism. The recently developed CRISPR/Cas9-based barcoding method is, although highly promising, difficult to scale up because it relies on exogenous barcoding sequences that are engineered into the genome. In this study, we characterized 78 high-quality endogenous sites in the zebrafish genome that can be used as CRISPR/Cas9-based barcoding sites. The 78 sites are all highly expressed in most of the cell types according to single-cell RNA sequencing (scRNA-seq) data. Hence, the barcoding information of the 78 endogenous sites is recovered by the available scRNA-seq platforms, enabling simultaneous characterization of cell type and cell lineage information.

Magnitude of modulation of gene expression in aneuploid maize depends on the extent of genomic imbalance

Adam F. Johnson, Jie Hou, Hua Yang, Xiaowen Shi, Chen Chen, Md Soliman Islam, Tieming Ji, Jianlin Cheng, James A. Birchler

2020, 47(2): 93-103. doi: 10.1016/j.jgg.2020.02.002

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Abstract:
Aneuploidy has profound effects on an organism, typically more so than polyploidy, and the basis of this contrast is not fully understood. A dosage series of the maize long arm of chromosome 1 (1L) was used to compare relative global gene expression in different types and degrees of aneuploidy to gain insights into how the magnitude of genomic imbalance as well as hypoploidy affects global gene expression. While previously available methods require a selective examination of specific genes, RNA sequencing provides a whole-genome view of gene expression in aneuploids. Most studies of global aneuploidy effects have concentrated on individual types of aneuploids because multiple dose aneuploidies of the same genomic region are difficult to produce in most model genetic organisms. The genetic toolkit of maize allows the examination of multiple ploidies and 1–4 doses of chromosome arms. Thus, a detailed examination of expression changes both on the varied chromosome arms and elsewhere in the genome is possible, in both hypoploids and hyperploids, compared with euploid controls. Previous studies observed the inverse trans effect, in which genes not varied in DNA dosage were expressed in a negative relationship to the varied chromosomal region. This response was also the major type of changes found globally in this study. Many genes varied in dosage showed proportional expression changes, though some were seen to be partly or fully dosage compensated. It was also found that the effects of aneuploidy were progressive, with more severe aneuploids producing effects of greater magnitude.

Both combinatorial K4me0-K36me3 marks on sister histone H3s of a nucleosome are required for Dnmt3a-Dnmt3L mediated de novo DNA methylation

Ting Gong, Xin Gu, Yu-Ting Liu, Zhen Zhou, Ling-Li Zhang, Yang Wen, Wei-Li Zhong, Guo-Liang Xu, Jin-Qiu Zhou

2020, 47(2): 105-114. doi: 10.1016/j.jgg.2019.12.006

Abstract (67) HTML PDF (2)

Abstract:
A nucleosome contains two copies of each histone H2A, H2B, H3 and H4. Histone H3 K4me0 and K36me3 are two key chromatin marks forde novo DNA methylation catalyzed by DNA methyltransferases in mammals. However, it remains unclear whether K4me0 and K36me3 marks on both sister histone H3s regulate de novo DNA methylation independently or cooperatively. Here, taking advantage of the bivalent histone H3 system in yeast, we examined the contributions of K4 and K36 on sister histone H3s to genomic DNA methylation catalyzed by ectopically co-expressed murine Dnmt3a and Dnmt3L. The results show that lack of both K4me0 and K36me3 on one sister H3 tail, or lack of K4me0 and K36me3 on respective sister H3s results in a dramatic reduction of 5mC, revealing a synergy of two sister H3s in DNA methylation regulation. Accordingly, the Dnmt3a or Dnmt3L mutation that disrupts the interaction of ^Dnmt3aADD domain-H3K4me0, ^Dnmt3LADD domain-H3K4me0, or ^Dnmt3aPWWP domain-H3K36me3 causes a significant reduction of DNA methylation. These results support the model that each heterodimeric Dnmt3a-Dnmt3L reads both K4me0 and K36me3 marks on one tail of sister H3s, and the dimer of heterodimeric Dnmt3a-Dnmt3L recognizes two tails of sister histone H3s to efficiently execute de novo DNA methylation.

Identification of potential cross-protective epitope between a new type of coronavirus (2019-nCoV) and severe acute respiratory syndrome virus

Tianyi Qiu, Tiantian Mao, Yuan Wang, Mengdi Zhou, Jingxuan Qiu, Jianwei Wang, Jianqing Xu, Zhiwei Cao

2020, 47(2): 115-117. doi: 10.1016/j.jgg.2020.01.003

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Abstract:

Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines

Xin Liu, Xiu-Jie Wang

2020, 47(2): 119-121. doi: 10.1016/j.jgg.2020.02.001

Abstract (357) HTML PDF (36)

Abstract:

2020 Vol. 47, No. 2