Identification of a Distal Regulatory Element of the Human Neuroglobin Gene (#208)
Neuroglobin (NGB) is a neuro-protective gene that alleviates the damage exerted by oxidative stress, stroke and Alzheimer’s disease. Its expression is only found in a limited number of cell types including neurons and retina. We hypothesized that the cell type-specific expression pattern of the NGB gene is mediated by distal regulatory elements like enhancers. By chromosome conformation capture, we identified that in the neuroblastoma cell line SH-SY5Y, two distal fragments physically interacted with the NGB gene from -70kb upstream and +100kb downstream respectively. The UCSC genome browser shows there were DNaseI hypersensitive sites and transcription factor binding sites in these fragments. A region of the upstream fragment with these active chromatin marks demonstrated cell type-specific enhancer activity towards NGB gene promoter. GATA-2 was shown to be binding to this region and contributing to its enhancer function. Knockdown of GATA-2 or deletion of the region caused a dramatic decrease of NGB expression. Therefore, we conclude that the region is a novel distal regulatory element which governs the cell type-specific expression of the NGB gene through loop formation. This is the first to identify a distal regulatory element of the gene. The discovery may be relevant to the development of therapeutic or preventive approaches against various neurological diseases.