Journal of Genetics and Genomics

Identification of a TSPY co-expression network associated with DNA hypomethylation and tumor gene expression in somatic cancers

Tatsuo Kido, Yun-Fai Chris Lau

2016, 43(10): 577-585. doi: 10.1016/j.jgg.2016.09.003

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Abstract:
Testis specific protein Y-encoded (TSPY) is a Y-located proto-oncogene predominantly expressed in normal male germ cells and various types of germ cell tumor. Significantly, TSPY is frequently expressed in somatic cancers including liver cancer but not in adjacent normal tissues, suggesting that ectopic TSPY expression could be associated with oncogenesis in non-germ cell cancers. Various studies demonstrated that TSPY expression promotes growth and proliferation in cancer cells; however, its relationship to other oncogenic events in TSPY-positive cancers remains unknown. The present study seeks to correlate TSPY expression with other molecular features in clinical cancer samples, by analyses of RNA-seq transcriptome and DNA methylation data in the Cancer Genome Atlas (TCGA) database. A total of 53 genes, including oncogenic lineage protein 28 homolog B (LIN28B) gene and RNA-binding motif protein Y-linked (RBMY) gene, are identified to be consistently co-expressed with TSPY, and have been collectively designated as the TSPY co-expression network (TCN). TCN genes were simultaneously activated in subsets of liver hepatocellular carcinoma (30%) and lung adenocarcinoma (10%) regardless of pathological stage, but only minimally in other cancer types. Further analysis revealed that the DNA methylation level was globally lower in the TCN-active than TCN-silent cancers. The specific expression and methylation patterns of TCN genes suggest that they could be useful as biomarkers for the diagnosis, prognosis and clinical management of cancers, especially those for liver and lung cancers, associated with TSPY co-expression network genes.

Targeted methylation sequencing reveals dysregulated Wnt signaling in Parkinson disease

Lusi Zhang, Jie Deng, Qian Pan, Yan Zhan, Jian-Bing Fan, Kun Zhang, Zhuohua Zhang

2016, 43(10): 587-592. doi: 10.1016/j.jgg.2016.05.002

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Abstract:
Parkinson disease (PD) is a progressive neurodegenerative movement disorder. Both environmental and genetic factors play important roles in PD etiology. A number of environmental toxins cause parkinsonism in human and animal models. Genetic studies of rare early onset familial PD cases resulted in identification of disease-linked mutations in multiple genes. Nevertheless, the potential interaction between environment and genetics in PD pathogenesis remains largely unknown. We hypothesized that environmental factors induce abnormal epigenetic regulation that is involved in the pathogenesis of both familial and sporadic PD. We determined the global methylation status of 80,000–110,000 CpG sites in each of the five sporadic PD patient brains and five age and postmodern interval matched control brains utilizing bisulfite padlock sequencing. Multiple genes involved in neurogenesis, particularly the ones in the Wnt signaling pathway, were hypermethylated in PD brains compared to their matched control brains. Consistent with the DNA methylation changes, marked reduction of protein expression was observed for four Wnt and neurogenesis related genes (FOXC1, NEURG2, SPRY1, and CTNNB1) in midbrain dopaminergic (DA) neurons of PD. The treatment of low concentration of 1-methyl-4-phenylpyridinium (MPP⁺) for cells resulted in downregulation of Wnt related genes. The study revealed an important link between the epigenetic disregulation of Wnt signaling and the pathogenesis and progression of PD.

Cebpα is essential for the embryonic myeloid progenitor and neutrophil maintenance in zebrafish

Yimei Dai, Lu Zhu, Zhibin Huang, Minyu Zhou, Wan Jin, Wei Liu, Mengchang Xu, Tao Yu, Yiyue Zhang, Zilong Wen, Wangjun Liao, Wenqing Zhang

2016, 43(10): 593-600. doi: 10.1016/j.jgg.2016.09.001

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Abstract:
In vertebrates, myeloid cells arise from multiple waves of development: the first or embryonic wave of myelopoiesis initiates early from non-hematopoietic stem cell (HSC) precursors and gives rise to myeloid cells transiently during early development; whereas the second or adult wave of myelopoiesis emerges later from HSCs and produces myeloid cells continually during fetal and adult life. In the past decades, a great deal has been learnt about the development of myeloid cells from adult myelopoiesis, yet the genetic network governing embryonic myelopoiesis remains poorly defined. In this report, we present an in vivo study to delineate the role of Cebpα during zebrafish embryonic myelopoiesis. We show that embryonic myelopoiesis in cebpα-deficient zebrafish mutants initiates properly but fails to produce macrophages and neutrophils. The lack of macrophages and neutrophils in the mutants is largely attributed to the cell cycle arrest of embryonic myeloid progenitors, resulting in the impairment of their maintenance and subsequent differentiation. We further show that Cebpα, perhaps acting cooperatively with Runx1, plays a critical role in embryonic neutrophil maintenance. Our findings reveal a new role of Cebpα in embryonic myelopoiesis.

OspTAC2 encodes a pentatricopeptide repeat protein and regulates rice chloroplast development

Dekai Wang, Heqin Liu, Guowei Zhai, Liangsheng Wang, Jianfeng Shao, Yuezhi Tao

2016, 43(10): 601-608. doi: 10.1016/j.jgg.2016.09.002

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Abstract:
Functional chloroplast generation depends on the precise coordination of gene expression between the plastid and the nucleus and is essential for plant growth and development. In this study, a rice (Oryza sativa) mutant that exhibited albino and seedling-lethal phenotypes was isolated from a⁶⁰Co-irradiated rice population. The mutant gene was identified as an ortholog of the Arabidopsis plastid transcriptionally active chromosome protein 2 (pTAC2) gene, and the mutant strain was designated osptac2. Sequence and transcription analyses showed that OspTAC2 encodes a putative chloroplast protein consisting of 10 pentratricopeptide repeat (PPR) domains and a C-terminal small MutS-related (SMR) domain. Cytological observations via microscopy showed that the OspTAC2-green fluorescent fusion protein is localized in the chloroplasts. Transmission electron microscopy revealed that the chloroplast of the osptac2 mutant lacks an organized thylakoid membrane. The transcript levels of all investigated PEP (plastid-encoded RNA polymerase)-dependent genes were dramatically reduced in the osptac2 mutant, whereas the transcript levels of NEP (nuclear-encoded polymerase)-dependent genes were increased. These results suggest that OspTAC2 plays a critical role in chloroplast development and indicate that the molecular function of the OspTAC2 gene is conserved in rice and Arabidopsis.

Variations in mesenchymal-epithelial transition-related transcription factors during reprogramming of somatic cells from different germ layers into iPSCs

Xiaoyin Lu, Yukai Wang, Long Yan, Libin Wang, Wei Li, Hongmei Wang

2016, 43(10): 609-612. doi: 10.1016/j.jgg.2016.04.001

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Abstract:

Zebrafish Cdh5 negatively regulates mobilization of aorta-gonad-mesonephros-derived hematopoietic stem cells

Ping Meng, Yongxiang Liu, Xiaohui Chen, Wenqing Zhang, Yiyue Zhang

2016, 43(10): 613-616. doi: 10.1016/j.jgg.2016.08.003

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Abstract:

The rising zebrafish research in China: Meeting report of the 3rd Chinese Zebrafish Principal Investigator Meeting & the Inaugural Meeting of China Zebrafish Society

Dongyuan Ma, Yuanyuan Xue, Yifan Zhang, Yonghua Sun, Anming Meng, Feng Liu

2016, 43(10): 617-620. doi: 10.1016/j.jgg.2016.10.001

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Abstract:

2016 Vol. 43, No. 10