Mechanisms of Gene Regulation in Chlamydia

衣原体基因调控机制

• 批准号: 7065196
• 负责人: P Scott Hefty
• 金额: $ 2.23万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7065196
• 关键词: Chlamydiaceae; DNA directed RNA polymerase; DNA footprinting; bacterial genetics; binding sites; chlamydial disease; gene expression; genetic promoter element; genetic regulation; immunoregulation; microarray technology; nucleoproteins; pathologic process; polymerase chain reaction; postdoctoral investigator; protein binding; transcription factor; virulence

DESCRIPTION (provided by applicant): Chlamydia species are the etiological agent for a diverse spectrum of human diseases that include ocular, pulmonary, lymphatic, cardiac and/or genital manifestations. Chlamydia is obligate intracellular pathogens that undergo a complex and unique developmental life cycle that is intrinsically linked to chlamydial pathogenesis. Numerous genes have been identified that are expressed primarily at specific stages of the developmental cycle. A global analysis of chlamydial gene expression during the developmental cycle demonstrates that 22% of the genes are temporally regulated and many of these gene products play key role(s) in the chlamydial developmental cycle and are likely virulence determinants. In prokaryotes, the primary stage of gene regulation is governed by transcriptional initiation. Sigma (G) factors are essential for the initiation of transcription and coordinate the expression of subsets of genes based on the recognition of specific promoter regions. Chlamydia encode three sigma factors, Sigma 68, the primary Sigma factor and two alternative Sigma factors, Sigma 28 and Sigma 54. While data support that Sigma 66 is responsible for the transcription of most constitutively-expressed genes, the role of Sigma 28 and Sigma 54 are currently unknown. This proposal is designed to analyze the hypothesis that Sigma 28 and Sigma 54 direct transcription of developmental stage-specific genes and virulence determinants. These stage-specific genes include but are not limited to; type III secretion systems and effector molecules, transcription factors and DNA compaction proteins. Very little is known about the cis- and trans-acting elements involved in chlamydial gene regulation and data generated during this study will provide a molecular basis for the specific mechanisms of gene regulation in Chlamydia.

描述（由申请人提供）：衣原体物种是各种人类疾病的病因学药，包括眼，肺，淋巴，心脏和/或生殖器表现。衣原体是义务的细胞内病原体，经历了复杂而独特的发育生命周期，与衣原体发病机构本质上有关。已经确定了许多基因，这些基因主要在发育周期的特定阶段表达。在发育周期期间对衣原体基因表达的全球分析表明，22％的基因受到时间调节，其中许多基因产物在衣原体发育周期中起关键作用，并且可能是毒力决定因素。在原核生物中，基因调节的主要阶段受转录启动的控制。 Sigma（g）因子对于基于特定启动子区域的识别而启动转录和协调基因子集的表达至关重要。衣原体编码三个Sigma因子，Sigma 68，主要的Sigma因子和两个替代Sigma因子Sigma 28和Sigma 54。尽管Sigma 66的数据支持是造成大多数组成型表达基因的转录，但Sigma 28和Sigma 54的作用是目前尚不清楚的。该建议旨在分析Sigma 28和Sigma 54发育阶段特异性基因和毒力决定因素的直接转录的假设。这些特定阶段的基因包括但不限于； III型分泌系统和效应分子，转录因子和DNA压实蛋白。对于参与衣原体基因调节的顺式和反式作用元件，本研究中产生的数据将为衣原体中基因调节的特定机制提供分子基础。