Identification of a Distal Regulatory Element of the Human Neuroglobin Gene — ASN Events

Identification of a Distal Regulatory Element of the Human Neuroglobin Gene (#208)

Kin Tung Tam 1 2 , Alistair Forrest 1 , Kian Cheng Tan-Un 2
  1. Harry Perkins Institute of Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, WA, Australia
  2. School of Biological Sciences, The University of Hong Kong, Hong Kong

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.

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