Biomedical subjects

Jia L Song

Publications and source records attributed to Jia L Song.

6 recordsLinked to original sources

PubMed2006

Oogenesis: single cell development and differentiation.

Oocytes express a unique set of genes that are essential for their growth, for meiotic recombination and division, for storage of nutrients, and for fertilization. We have utilized the newly sequenced genome of Strongylocentrotus purpuratus to identify genes that help the oocyte accomplish each of these tasks. This study emphasizes four classes of genes that are specialized for oocyte function: (1) Transcription factors: many of these factors are not significantly expressed in embryos, but are shared by other adult tissues, namely the ovary, testis, and gut. (2) Meiosis: A full set of meiotic genes is present in the sea urchin, including those involved in cohesion, in synaptonemal complex formation, and in meiotic recombination. (3) Yolk uptake and storage: Nutrient storage for use during early embryogenesis is essential to oocyte function in most animals; the sea urchin accomplishes this task by using the major yolk protein and a family of accessory proteins called YP30. Comparison of the YP30 family members across their conserved, tandem fasciclin domains with their intervening introns reveals an incongruence in the evolution of its major clades. (4) Fertilization: This set of genes includes many of the cell surface proteins involved in sperm interaction and in the physical block to polyspermy. The majority of these genes are active only in oocytes, and in many cases, their anatomy reflects the tandem repeating interaction domains essential for the function of these proteins. Together, the expression profile of these four gene classes highlights the transitions of the oocyte from a stem cell precursor, through stages of development, to the clearing and re-programming of gene expression necessary to transition from oocyte, to egg, to embryo.

Animals↗

PubMed2005

How to make an egg: transcriptional regulation in oocytes.

The oocyte is a highly differentiated cell. It makes organelles specialized to its unique functions and progresses through a series of developmental stages to acquire a fertilization competent phenotype. This review will integrate the biology of the oocyte with what is known about oocyte-specific gene regulation and transcription factors involved in oocyte development. We propose that oogenesis is reliant on a dynamic gene regulatory network that includes oocyte-specific transcriptional regulators.

Animals↗

PubMed2005

Drug-induced regulation of the MDR1 promoter in Candida albicans.

Resistance of Candida albicans to azole antifungal drugs is mediated by two types of efflux pumps, encoded by the MDR1 gene and the CDR gene family. MDR1 mRNA levels in a susceptible clinical isolate are induced by benomyl (BEN) but not by other drugs previously shown to induce MDR1. To monitor MDR1 expression under several conditions, the MDR1 promoter was fused to the Renilla reniformis luciferase reporter gene (RLUC). The promoter was monitored for its responses to four oxidizing agents, five toxic hydrophobic compounds, and an alkylating agent, all shown to induce major facilitator pumps in other organisms. Deletion constructs of the MDR1 promoter were used to analyze the basal transcription of the promoter and its responses to the toxic compound BEN and the oxidizing agent tert-butyl hydrogen peroxide (T-BHP). The cis-acting elements in the MDR1 promoter responsible for induction by BEN were localized between -399 and -299 upstream of the start codon. The cis-acting elements responsible for MDR1 induction by T-BHP were localized between -601 and -500 upstream of the start codon. The T-BHP induction region contains a sequence that resembles the YAP1-responsive element (YRE) in Saccharomyces cerevisiae. This Candida YRE was placed upstream of a noninducible promoter in the luciferase construct, resulting in an inducible promoter. Inversion or mutation of the 7-bp YRE eliminated induction. Many of the drugs used in this analysis induce the MDR1 promoter at concentrations that inhibit cell growth. These analyses define cis-acting elements responsible for drug induction of the MDR1 promoter.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

The Candida albicans lanosterol 14-alpha-demethylase (ERG11) gene promoter is maximally induced after prolonged growth with antifungal drugs.

The azole antifungal drugs that target lanosterol 14-alpha-demethylase, encoded by the ERG11 gene, are used to treat a variety of infections caused by Candida albicans. Azoles are known to induce expression of ERG11 mRNA. The ERG11 promoter was cloned 5' of the luciferase-coding region, and the induction of ERG11 expression by azoles was monitored by luciferase assays. Maximal induction of the ERG11 promoter by azoles occurs not during logarithmic growth but after the diauxic shift and requires azoles to be present throughout logarithmic growth. The effects of pH, carbon source, and aerobic or anaerobic growth on induction of the ERG11 promoter by azoles were analyzed. Treatment with terbinafine and fenpropimorph, which target other enzymes in the ergosterol biosynthetic pathway, also resulted in a delayed induction of ERG11 promoter activity. Nascent sterol synthesis was shown to parallel ERG11 promoter activity, and total sterols were reduced coincident with the timing of ERG11 promoter activation. These results as a whole suggest that expression of the ERG11 promoter is regulated in response to sterol depletion.

Alleles↗

PubMed2003

Antifungal activity of fluconazole in combination with lovastatin and their effects on gene expression in the ergosterol and prenylation pathways in Candida albicans.

The sterol pathway in Candida albicans is the target for several classes of antifungal drugs. Intermediates in the sterol pathway are involved in ergosterol synthesis, prenylation and dolichol synthesis. This study examines gene expression of the sterol pathway in response to lovastatin, an inhibitor of HMG-CoA reductase (Hmg1p), and fluconazole, an inhibitor of 14 alpha-lanosterol demethylase (Erg11p). Minimum inhibitory concentration (MIC) studies indicated that lovastatin acts synergistically with fluconazole in vitro. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) results indicated that genes in the early part of the sterol pathway, such as HMG1 and ERG20, did not alter expression in the presence of both lovastatin and fluconazole, whereas genes in the later part of the sterol pathway, such as ERG9 and ERG11, had increased expression in response to these drugs in mid-logarithmic growth. Genes involved in prenylation, such as RAM1 and RAM2, also respond to these drugs in mid-logarithmic growth, although another prenylation gene, CDC43, was not affected. After 24 h of growth, the relative expression of ERG20, ERG9, and ERG11 remained unchanged or increased in the presence of both drugs, while all other genes decreased in expression under all drug treatments.

Base Sequence↗

PubMed2003

RAM2: an essential gene in the prenylation pathway of Candida albicans.

Prenylation is a post-translational protein modification process that results in correct protein localization to membranes in the cell. It is mediated by at least three prenyltransferases (PTFs) in eukaryotic cells. The RAM2 gene encodes the common alpha-subunit of two PTFs, farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I). In this study, the RAM2 gene of the prenylation pathway in the opportunistic pathogen Candida albicans was analysed. The heterozygote trisomy test was used to demonstrate that RAM2 is essential to the viability of C. albicans. RAM2 mRNA in the yeast and hyphae growth states was not detected by Northern blot analysis, but was detected by RT-PCR. Drugs that inhibit mammalian PTFs do not alter Candida cell growth, but they do inhibit FTase and GGTase I activities in cell-free enzyme assays. The data from genetic studies and cell-free enzyme assays suggest that the drugs may not have access to the Candida cytoplasm. The regulation of PTF subunits was also examined in a strain in which RAM2 was under the control of a regulable promoter. Overall, this study demonstrated that RAM2 is essential to C. albicans, indicating that protein prenylation is an indispensable cellular process in this yeast.

Alkyl and Aryl Transferases↗