Functional analysis of Fam72

Abstract

Brain development and repair largely depend on neural stem cells (NSCs). Here, I suggest that two genes, Srgap2 (SLIT-ROBO Rho GTPase activating protein 2) and Fam72 (family with sequence similarity to 72), constitute a single, NSC-specific,; -Srgap2–Fam72-; master gene pair. This gene pair has a dual, commonly used, intergenic region (IGR) promotor, which is a prerequisite in controlling human brain plasticity. I applied fluorescent cellular microscopy and fluorescence-activated cell sorting (FACS) to assess; master gene IGR promotor activity upon stimulation with two contrary growth factors: epidermal growth factor (Egf, a mitotic growth factor) and nerve growth factor (Ngf, a differentiation growth factor). I found that Egf and Ngf acted on the same IGR gene promotor element of the; master gene to mediate cell proliferation and differentiation, respectively. Egf activated Fam72 transcription and cell proliferation while Ngf mediated Srgap2 expression and neuronal survival and differentiation. My data provide new insights into the specific regulation of the; master gene with its dual IGR promotor that controls two reverse-oriented genes located on opposite DNA strands. This structure represents a novel paradigm for controlling transcription of divergent genes in regulating NSC gene expression. This paradigm may allow for novel therapeutic approaches to restore or improve higher cognitive functions and cure cancers.