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 CONTENT
ABSTRACT
ACKNOWLEDGEMENTS
DEDICATION
TABLE OF CONTENT
LIST OF FIGURES
CHAPTER ONE
INTRODUCTION
CHAPTER TWO
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
CHAPTER THREE
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
CHAPTER FOUR
RESULTS
CHAPTER FIVE
DISCUSSION
6.1 Conclusions
6.2 Recommendations
REFERENCES
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