Distal Enhancer – Gene Interactions at the Lmo2 locus in Mouse Erythroid cells

Distal regulatory elements (DREs) have been identified upstream of the hematopoietic regulator Lim domain only 2 (Lmo2) gene in the human and mouse genomes. In this thesis I have investigated how these elements regulate Lmo2 transcription in erythroid cells. My results show that strong chromatin-chromatin interactions exist between the DREs and the Lmo2 gene promoter in erythroid cells. These interactions are absent from kidney cells that do not express Lmo2. Within the distal chromatin interaction cluster encompassing three of the DREs increased DNase I sensitivity, presence of high levels of H3K4me1, and binding of multiple transcription factors, p300, cohesin (RAD21) and CTCF are observed. CTCF bound regions are located between the farthest DRE and the neighboring Caprin1 promoter suggesting that CTCF insulates Caprin1 from the DREs. Hence, my data suggests that these DREs function through a chromatin looping mechanism supported by cohesin associated with CTCF and transcription factor bound regions.MAS