Organisation of transcriptomes : searching for regulatory DNA elements involved in the correlated expression of genomic neighbours

Abstract

Since the thesis that every gene acts as a single unit which transcription is solely regulated by promoter-binding transcription factors (TF) - irrespective of the surrounding genomic landscape - has been rejected, transcriptional regulation of genes has become a field of ever-growing complexity. Factors like the “state” of chromatin and DNA positioning inside the nucleus have been shown to have a major impact on the activation and repression of the transcription of genes. Furthermore it was discovered that the expression of individual adjacent genes in the genome is not independent, but genomic neighbours are co-expressed more often than what would be expected by chance. These neighbours form clusters of co-expressed genes that can be found all over the genome containing from two to several adjacent entities. In this thesis a possible explanation of this observation was investigated, namely the active alteration of chromatin state by possible interaction of transcription factors or other genomic features. Sequence analysis methods were used to search for possible DNA specific factors that could form “active chromatin hubs (ACH)” in the region of those o-expressed genes and therefore could lead to the revealed correlated expression. The thesis is based on our earlier analysis of the expression of genomic neighbours in mouse/human and proceeds these investigations