Genome-wide screen for cell growth regulators in fission yeast

ABSTRACT Gene duplication is considered an important evolutionary mechanism. Unlike many characterized species, the fission yeast Schizosaccharomyces pombe contains two paralogous genes, tup11 + and tup12 + , that encode transcriptional corepressors similar to the well-characterized budding yeast Tup1 protein. Previous reports have suggested that Tup11 and Tup12 proteins play redundant roles. Consistently, we show that the two Tup proteins can interact together when expressed at normal levels and that each can independently interact with the Ssn6 protein, as seen for Tup1 in budding yeast. However, tup11 − and tup12 − mutants have different phenotypes on media containing KCl and CaCl2. Consistent with the functional difference between tup11 − and tup12 − mutants, we identified a number of genes in genome-wide gene expression experiments that are differentially affected by mutations in the tup11 + and tup12 + genes. Many of these genes are differentially derepressed in tup11 − mutants and are over-represented in genes that have previously been shown to respond to a range of different stress conditions. Genes specifically derepressed in tup12 − mutants require the Ssn6 protein for their repression. As for Tup12, Ssn6 is also required for efficient adaptation to KCl- and CaCl2-mediated stress. We conclude that Tup11 and Tup12 are at least partly functionally diverged and suggest that the Tup12 and Ssn6 proteins have adopted a specific role in regulation of the stress response.

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Genome-Wide Methylation Analysis Identifies NOX4 and KDM5A as Key Regulators in Inhibiting Breast Cancer Cell Proliferation by Ginsenoside Rg3

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500702 ◽

2018 ◽

Vol 46 (06) ◽

pp. 1333-1355 ◽

Cited By ~ 11

Author(s):

Juyeon Ham ◽

Seungyeon Lee ◽

Hyunkyung Lee ◽

Dawoon Jeong ◽

Sungbin Park ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Cancer Cells ◽

Cancer Cell ◽

Growth Effect ◽

Breast Cancer Patients ◽

Ginsenoside Rg3 ◽

Methylation Analysis ◽

Genome Wide

Ginsenoside Rg3 is a key metabolite of ginseng and is known to inhibit cancer cell growth. However, the epigenetics of CpG methylation and its regulatory mechanism have yet to be determined. Genome-wide methylation analysis of MCF-7 breast cancer cells treated with Rg3 was performed to identify epigenetically regulated genes and pathways. The effect of Rg3 on apoptosis and cell proliferation was examined by a colony formation assay and a dye-based cell proliferation assay. The association between methylation and gene expression was monitored by RT-PCR and Western blot analysis. Genome-wide methylation analysis identified the “cell morphology”-related pathway as the top network. Rg3 induced late stage apoptosis but inhibited cell proliferation up to 60%. Hypermethylated TRMT1L, PSMC6 and NOX4 were downregulated by Rg3, while hypomethylated ST3GAL4, RNLS and KDM5A were upregulated. In accordance, downregulation of NOX4 by siRNA abrogated the cell growth effect of Rg3, while the effect was opposite for KDM5A. Notably, breast cancer patients with a higher expression of NOX4 and KDM5A showed poor and good prognosis of survival, respectively. In conclusion, Rg3 deregulated tumor-related genes through alteration of the epigenetic methylation level leading to growth inhibition of cancer cells.

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Control of hematopoietic cell growth regulators during mouse fetal development

Molecular and Cellular Biology ◽

10.1128/mcb.7.9.3361-3364.1987 ◽

1987 ◽

Vol 7 (9) ◽

pp. 3361-3364

Author(s):

M Azoulay ◽

C G Webb ◽

L Sachs

Keyword(s):

Gene Expression ◽

Cell Growth ◽

Growth Regulators ◽

Fetal Development ◽

Hematopoietic Cell ◽

Regulatory Proteins ◽

Colony Stimulating Factor ◽

Cell Lineages ◽

Stimulating Factor ◽

Extraembryonic Tissues

Gene expression for the four different growth-regulatory proteins for cells of the myeloid hematopoietic cell lineages was analyzed in mouse fetal and extraembryonic tissues at various stages of development. The macrophage growth inducer MGI-1M (colony-stimulating factor 1) was the only myeloid hematopoietic growth regulator detected as both mRNA and bioactive protein during fetal development. This regulator was produced predominantly in extraembryonic tissues, and the production of hematopoietic growth regulators in embryogenesis was regulated by transcriptional and posttranscriptional controls.

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