Journal of Genetics and Genomics

A snapshot of the Chinese SOL Project

Changbao Li, Jiuhai Zhao, Hongling Jiang, Yu Geng, Yuanyuan Dai, Huajie Fan, Dongfen Zhang, Jinfeng Chen, Fei Lu, Jinfeng Shi, Shouhong Sun, Jianjun Chen, Xiaohua Yang, Chen Lu, Mingsheng Chen, Zhukuan Cheng, Hongqing Ling, Ying Wang, Yongbiao Xue, Chuanyou Li

2008, 35(7): 387-390. doi: 10.1016/S1673-8527(08)60056-9

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Abstract:
In 2003, the International Solanaceae Project (SOL) was initiated by an international consortium of ten countries including Korea, China, the United Kingdom, India, the Netherlands, France, Japan, Spain, Italy and the United States. The first major effort of the SOL aimed to produce a DNA sequence map for euchromatin regions of 12 chromosomes of tomato (Solanum lycopersicum) before 2010. Here we present an update on Chinese effort for sequencing the euchromatin region of chromosome 3.

Future impact of integrated high-throughput methylome analyses on human health and disease

Lee M Butcher, Stephan Beck

2008, 35(7): 391-401. doi: 10.1016/S1673-8527(08)60057-0

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Abstract:
A spate of high-powered genome-wide association studies (GWAS) have recently identified numerous single-nucleotide polymorphisms (SNPs) robustly linked with complex disease. Despite interrogating the majority of common human variation, these SNPs only account for a small proportion of the phenotypic variance, which suggests genetic factors are acting in concert with non-genetic factors. Although environmental measures are logical covariants for genotype-phenotype investigations, another non-genetic intermediary exists: epigenetics. Epigenetics is the analysis of somatically-acquired and, in some cases, transgenerationally inherited epigenetic modifications that regulate gene expression, and offers to bridge the gap between genetics and environment to understand phenotype. The most widely studied epigenetic mark is DNA methylation. Aberrant methylation at gene promoters is strongly implicated in disease etiology, most notably cancer. This review will highlight the importance of DNA methylation as an epigenetic regulator, outline techniques to characterize the DNA methylome and present the idea of reverse phenotyping, where multiple layers of analysis are integrated at the individual level to create personalized digital phenotypes and, at a phenotype level, to identify novel molecular signatures of disease.

Tackling the epigenome in the pluripotent stem cells

Xiaodong Zhao, Yijun Ruan, Chia-Lin Wei

2008, 35(7): 403-412. doi: 10.1016/S1673-8527(08)60058-2

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Abstract:
Embryonic stem cells are unique in their abilities of self-renewal and to differentiate into many, if not all, cellular lineages. Transcriptional regulation, epigenetic modifications and chromatin structures are the key modulators in controlling such pluripotency nature of embryonic stem cell genomes, particularly in the developmental decisions and the maintenance of cell fates. Among them, epigenetic regulation of gene expression is mediated partly by covalent modifications of core histone proteins including methylation, phosphorylation and acetylation. Moreover, the chromatins in stem cell genome appear as a highly organized structure containing distinct functional domains. Recent rapid progress of new technologies enables us to take a global, unbiased and comprehensive view of the epigenetic modifications and chromatin structures that contribute to gene expression regulation and cell identity during diverse developmental stages. Here, we summarized the latest advances made by high throughput approaches in profiling epigenetic modifications and chromatin conformations, with an emphasis on genome-wide analysis of histone modifications and their implications in pluripotency nature of embryonic stem cells.

Epigenetic regulation of genes during development: A conserved theme from flies to mammals

Dasari Vasanthi, Rakesh K Mishra

2008, 35(7): 413-429. doi: 10.1016/S1673-8527(08)60059-4

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Abstract:
Eukaryotic genome is organized in form of chromatin within the nucleus. This organization is important for compaction of DNA as well as for the proper expression of the genes. During early embryonic development, genomic packaging receives variety of signals to eventually set up cell type specific expression patterns of genes. This process of regulated chromatinization leads to “cell type specific epigenomes”. The expression states attained during differentiation process need to be maintained subsequently throughout the life of the organism. Epigenetic modifications are responsible for chromatin dependent regulatory mechanism and play a key role in maintenance of the expression state—a process referred to as cellular memory. Another key feature in the packaging of the genome is formation of chromatin domains that are thought to be structural as well as functional units of the higher order chromatin organization. Boundary elements that function to define such domains set the limits of regulatory elements and that of epigenetic modifications. This connection of epigenetic modification, chromatin structure and genome organization has emerged from several studies. Hox genes are among the best studied in this context and have led to the significant understanding of the epigenetic regulation during development. Here we discuss the evolutionarily conserved features of epigenetic mechanisms emerged from studies on homeotic gene clusters.

A stringent dual control system overseeing transcription and activity of the Cre recombinase for the liver-specific conditional gene knock-out mouse model

Yu Wu, Yinghua He, Hongyu Zhang, Xinlan Dai, Xiaoyu Zhou, Jun Gu, Guan Wang, Jingde Zhu

2008, 35(7): 431-439. doi: 10.1016/S1673-8527(08)60060-0

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Abstract:
Liver cancer is one of the most threatening diseases in Chinese population. Just like in other tissues, tumor initiation and development in liver involve multiple steps of genetic and epigenetic alterations with several unknown details. However, unlike in other tissues, a tissue specific inducible Cre recombinase system that allows temporal and spatial deletion of a target DNA fragment is still not available for in vivo functional gene annotation in hepatocytes. In our pursuit to establish such a mouse model, we designed a dual inducible Cre transgene system and tested it in cultured cells. By combining a CCAAT/enhancer binding protein β (C/EBP β) promoter derived Tet-off expression system and the estrogen receptor (ER) mediated functional control, we show a desirable profile of both hepatocyte-specificity and regulability of the Cre expression in a series of critical assessments in the cell culture system, which provides confidence in continuation of our ongoing pursuit in mouse.

Ectopic expression of soybean GmKNT1 in Arabidopsis results in altered leaf morphology and flower identity

Jun Liu, Da Ha, Zongming Xie, Chunmei Wang, Huiwen Wang, Wanke Zhang, Jinsong Zhang, Shouyi Chen

2008, 35(7): 441-449. doi: 10.1016/S1673-8527(08)60061-2

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Abstract:
Plant morphology is specified by leaves and flowers, and the shoot apical meristem (SAM) defines the architecture of plant leaves and flowers. Here, we reported the characterization of a soybean KNOX gene GmKNT1, which was highly homologous to Arabidopsis STM. The GmKNT1 was strongly expressed in roots, flowers and developing seeds. Its expression could be induced by IAA, ABA and JA, but inhibited by GA or cytokinin. Staining of the transgenic plants overexpressing GmKNT1-GUS fusion protein revealed that the GmKNT1 was mainly expressed at lobe region, SAM of young leaves, sepal and carpel, not in seed and mature leaves. Scanning electron microscopy (SEM) disclosed multiple changes in morphology of the epidermal cells and stigma. The transgenic Arabidopsis plants overexpressing the GmKNT1 showed small and lobed leaves, shortened internodes and small clustered inflorescence. The lobed leaves might result from the function of the meristems located at the boundary of the leaf. Compared with wild type plants, transgenic plants had higher expression of the SAM-related genes including the CUP, WUS, CUC1, KNAT2 and KNAT6. These results indicated that the GmKNT1 could affect multiple aspects of plant growth and development by regulation of downstream genes expression.

2008 Vol. 35, No. 7