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Published on: May 27, 2016
Regulation of human and mouse procathepsin E gene expression
M Cook1, R C Caswell, R J Richards
1School of Biosciences, Cardiff University, Wales, UK.
Abstract:
Cathepsin E is an intracellular aspartic proteinase that is considered to have a number of physiological roles including antigen processing. Quantitation of procathepsin E mRNA by LightCyclertrade mark technology indicated that the gene was transcribed in lung but not in kidney of both human and mouse origin. In contrast, the transcript was present in mouse spleen and alveolar macrophages but not in the counterpart tissue/cells from humans. Regulation of human and mouse procathepsin E gene expression was shown not to be influenced by the extent of CpG methylation but depended on the recognition of potential binding motifs in each promoter region by transcription factors such as GATA1, PU1 and YY1, as revealed by functional analysis using a series of promoter/luciferase reporter gene fusion constructs. Thus the extent to which the procathepsin E gene is expressed in a particular cell type may depend on the balance between the effects produced by positive-acting, cell-specific transcription factors such as GATA1 and PU1 and the negative influence of the ubiquitous YY1 factor. In this way, the relative abundance and influence of general and cell-specific transcription factors can govern the production of cathepsin E and thereby account for the sporadic cell and tissue distribution of this enzyme in different species.
Insights
Cathepsin E gene expression varies across human and mouse tissues, with regulation influenced by transcription factors like GATA1, PU1, and YY1, not CpG methylation.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Cathepsin E is an intracellular aspartic proteinase with diverse physiological roles, including antigen processing.
- Understanding the gene expression patterns and regulatory mechanisms of Cathepsin E is crucial for elucidating its functions.
Purpose of the Study:
- To investigate the tissue-specific expression of procathepsin E mRNA in humans and mice.
- To explore the regulatory mechanisms controlling human and mouse procathepsin E gene expression, focusing on promoter activity and transcription factors.
Main Methods:
- Quantitation of procathepsin E mRNA using LightCycler technology.
- Functional analysis of promoter regions using a series of promoter/luciferase reporter gene fusion constructs.
- Assessment of CpG methylation's influence on gene expression.
Main Results:
- Procathepsin E mRNA was detected in human and mouse lung, mouse spleen, and mouse alveolar macrophages, but not in kidney or human alveolar macrophages.
- Gene expression was not influenced by CpG methylation.
- Functional analysis revealed that transcription factors GATA1, PU1, and YY1 bind to promoter regions, regulating gene expression.
Conclusions:
- The cell and tissue-specific distribution of Cathepsin E is governed by the interplay of cell-specific transcription factors (GATA1, PU1) and a ubiquitous repressor factor (YY1).
- The balance of these transcription factors dictates Cathepsin E production, explaining its varied presence across different cell types and species.
