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Role of ESE-2 Ets factor in Epithelial biology

ESE-2 Ets 因子在上皮生物学中的作用

基本信息

批准号：
7216288
负责人：
SATRAJIT SINHA
金额：
$ 23.88万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7216288
关键词：
Affect Binding Binding Sites Biochemical Biological Biological Assay Biological Models Biological Process Biology Cell Differentiation process Cell Proliferation Cells Cessation of life Condition Consensus DNA DNA Binding DNA Sequence DNA-Binding Proteins Deoxyribonuclease I Development Differentiation and Growth Disease Elements Embryo Epidermis Epithelial Epithelial Cell Proliferation Epithelial Cells Epithelium Equilibrium Exhibits Family Gene Expression Gene Expression Profile Gene Targeting Genes Genetic Transcription Goals Knock-out Knockout Mice Knowledge Lead Localized Malignant Neoplasms Mediating Modeling Molecular Mus Nuclear Physiological Play Process Property Protein Analysis Protein Isoforms Proteins Recombinants Regulation Regulatory Element Repression Research Personnel Role Shapes Site Skin Structure Technology Testing Tissues Trans-Activators Transcriptional Activation Transcriptional Regulation Transfection Work cell type embryonic stem cell in vivo insight keratinocyte mRNA Expression mouse model novel programs promoter research study stem tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): The balance between cell proliferation and differentiation is critical to the physiological function of the epithelium and is therefore well regulated, in part by transcription factors that control gene expression during these processes. Previous work has suggested that the ESE family of Ets transcription factors may play an important role in epithelial development and functional specialization. We have utilized skin keratinocytes as a model system to examine the biological role of ESE-2. Our preliminary studies characterizing the ESE-2 promoter have led to identification of a novel nuclear factor, KSF, that among all the cell types tested is restricted to keratinocytes and is important for the promoter activity. In order to gain insights into the biological function of ESE-2, we have begun a structure-function analysis of the protein. We show that recombinant ESE-2 isoforms can bind to known Ets-binding sites. However, the optimum DNA target for ESE-2 including the core motif and the flanking sequences remains to be determined. In order to define the in vivo role of ESE-2 and identify its target genes we have successfully targeted the ESE-2 gene in embryonic stem cell (ES) clones. Our studies indicate that a thorough analysis of the mechanism of action of ESE-2, its biological role and the identification of factors that regulate its expression should lead to a better understanding of epithelial cell differentiation process. Therefore, in the present proposal we seek to identify and characterize the regulatory factors that control the epithelium-specific expression of ESE-2, including the KSF protein (Aim 1), to perform a comprehensive structure-function analysis of all ESE-2 isoforms to identify their consensus binding sites and to characterize potential activation or repression domains that are critical for their specific roles in skin epidermis (Aim 2), and to employ an in vivo knock out model system to assess the biological role of ESE-2 during epithelial development and differentiation and to identify ESE-2 targets (Aim 3). Our studies will provide the tools to investigate the molecular mechanisms by which ESE-2 controls and shapes epithelial growth and differentiation and to identify important modulators of these processes. The studies proposed will thus provide fundamental insights into the biology of epithelial cells during both normal physiological conditions and abnormal pathological states. Such knowledge is vital to developing new therapies and cures for a wide array of diseases that afflict the epithelial cells including cancers.

描述（由申请人提供）：