The interaction between transcriptional factors and cis-regulatory DNA element has given rise to the diversity in the expression of eukaryotic gene. Prdm15 gene is known to be expressed in the brain throughout development of mouse and zebrafish however; there are no known enhancer(s) for this gene in the brain. The aim of this study was to identify brain specific enhancer(s) for the gene Prdm15 during brain development. The VISTA enhancer browser and Encyclopedia of DNA Elements (ENCODE) data were used in this study to determine our candidate brain enhancer. The VISTA enhancer browser was used to quest for cis-regulatory element(s) in the environs of Prdm15 by comparative genomics and only one candidate enhancer we designated Prdm15 control element 1(PCE1) was identified downstream of the gene. PCE1 was found to be conserved in organisms such as chicken, zebrafish, rhesus, chimp, dog and cow. To ascertain if PCE1 is a brain enhancer, we delineated PCE1 using brain-specific enhancer chromatin modification signatures H3K4me1 and H3K27ac in the ENCODE data and they showed enrichment for PCE1. In conclusion, our data set revealed that only one brain candidate enhancer (PCE1) exist for Prdm15 and that this brain enhancer for Prdm15 will help in identifying important upstream specific transcription factors of PrdmI5 during brain development.
Table of Contents
1. Introduction
2. Literature Review
2.1 Prdm gene family
2.2 Cis-regulatory architecture of the genome
2.3 Transcriptional regulation by enhancers
2.3.1 Transcriptional enhancers
2.3.2 Deregulation of enhancer function in human disease
2.4 Chromatin signatures in different enhancer states
2.4.1 Interaction between transcription factors and chromatin
2.5 Genome wide identification of enhancer element
3. Materials and Methods
3.1 Search for cis-regulatory element(s) in the vicinity of Prdm15 by comparative genomics
3.2 Delineation of candidate brain enhancers of Prdm15 using brain-specific enhancer chromatin modification signatures
4. Results
5. Discussion
6.1 Conclusions
6.2 Recommendations
Research Objectives and Themes
The primary objective of this study is to identify and characterize brain-specific enhancers for the Prdm15 gene, which is known to be expressed during brain development but lacks well-defined regulatory elements. The research addresses the knowledge gap regarding how non-coding regulatory sequences contribute to gene expression patterns in the brain.
- Identification of conserved non-coding regulatory sequences near the Prdm15 locus.
- Use of comparative genomics across various species to pinpoint candidate enhancer elements.
- Application of ENCODE data to profile brain-specific chromatin modification signatures (H3K4me1 and H3K27ac).
- Evaluation of the functional relevance of identified control elements in tissue-specific gene regulation.
Excerpt from the Book
Cis-regulatory architecture of the genome
Gene expression is regulated through the interacted action of promoter proximal element and many cis-regulatory element DNA element (enhancers, insulators and silencers) that are located at greater distance from the transcription start site (Lenhard et al.,2012; Levine,2010). These elements are located far upstream or downstream or inside gene and even inside adjacent gene (Wijgerde et al., 1995). Hence it is not always obvious which element control which gene and the identification of essential distal element has to be accomplished by experimental means using genetic manipulation. Also, each of these regulatory modules performs a specific function in a specific cell type or at a particular stage in development (Spitz et al., 2003). Many key developmental cis-regulatory element like enhancers act not only on their biologically relevant target gene but also on unrelated neighboring genes (Zuniga, 2004). According to Ruf (2011), among these elements enhancers and their associated transcriptional factors have a leading role in the initiation of gene expression.
Summary of Chapters
Introduction: Outlines the fundamental role of cis-regulatory elements in gene expression and highlights the lack of known enhancers for the Prdm15 gene in the brain.
Literature Review: Provides a comprehensive overview of the Prdm gene family, enhancer architecture, and the use of chromatin signatures to predict enhancer activity.
Materials and Methods: Describes the bioinformatics approach using VISTA enhancer browser for conservation analysis and ENCODE data for chromatin signature profiling.
Results: Presents the discovery of the Prdm15 control element (PCE1) and demonstrates its conservation across species and its specific chromatin marks in the cerebellum.
Discussion: Interprets the findings by linking the identified PCE1 element to potential regulatory roles for Prdm15, while excluding it from the regulation of the neighboring Ripk4 gene.
Conclusions and Recommendations: Summarizes the findings and suggests future experimental validations, such as cloning the enhancer for reporter assays.
Keywords
Prdm15, Gene expression, Cis-regulatory elements, Enhancers, Brain development, Chromatin signatures, H3K4me1, H3K27ac, Comparative genomics, VISTA enhancer browser, ENCODE, Bioinformatics, Transcriptional regulation, Epigenetics, PCE1.
Frequently Asked Questions
What is the primary focus of this dissertation?
The research focuses on identifying and delineating candidate brain-specific enhancers that regulate the Prdm15 gene during brain development.
Which gene family does Prdm15 belong to?
Prdm15 is part of the Prdm gene family, which is characterized by an N-terminal positive regulatory (PR) domain involved in cellular proliferation and differentiation.
What is the main goal of the research?
The goal is to determine if the identified candidate enhancer (PCE1) acts as a brain-specific regulatory element for Prdm15, given that no such enhancers were previously known.
Which scientific methods were employed?
The study used comparative genomics via the VISTA enhancer browser and the analysis of chromatin modification signatures (H3K4me1 and H3K27ac) obtained from ENCODE databases.
What is covered in the main body of the work?
The work covers the general theory of enhancers, the role of the Prdm family, the methodology for finding regulatory elements, the results of the bioinformatics analysis, and a discussion of the identified PCE1 element.
Which keywords best describe this research?
Key terms include Prdm15, gene regulation, enhancer, chromatin signatures, bioinformatics, and developmental biology.
What is the significance of the PCE1 element?
PCE1 is identified as a conserved, brain-specific candidate enhancer located downstream of Prdm15, showing distinct enrichment for active enhancer chromatin marks in the cerebellum.
How did the author rule out PCE1 as a regulator for the Ripk4 gene?
The author performed a comparative analysis in bone marrow tissue, where Ripk4 is expressed but Prdm15 is not, and found no enrichment for enhancer-associated chromatin marks at the PCE1 location, suggesting it is tissue-specific to the brain.
- Quote paper
- Michael Adu (Author), 2018, Cis-regulatory elements underlying Prdm15 gene during brain development, Munich, GRIN Verlag, https://www.grin.com/document/1169011
