KUTZNER, ARNE HOLGER
2019-08-28T07:08:19Z
2019-08-28T07:08:19Z
2019-08
MOLECULAR NEUROBIOLOGY, v. 56 , NO 8 , Page. 5891-5899
0893-7648
1559-1182
https://link.springer.com/article/10.1007%2Fs12035-019-1486-5
https://repository.hanyang.ac.kr/handle/20.500.11754/110044
Brain development and repair largely depend on neural stem cells (NSCs). Here, we suggest that two genes, i.e., Srgap2 (SLIT-ROBO Rho GTPase-activating protein 2) and Fam72a (family with sequence similarity to 72, member A), constitute a single, NSC-specific, |-Srgap2-Fam72a-| master gene pair co-existing in reciprocal functional dependency. This gene pair has a dual, commonly used, intergenic region (IGR) promotor, which is a prerequisite in controlling human brain plasticity. We applied fluorescence cellular microscopy and fluorescence-activated cell sorting (FACS) to assess rat |-Srgap2-Fam72a-| master gene IGR promotor activity upon stimulation with two contrary growth factors: nerve growth factor (Ngf, a differentiation growth factor) and epidermal growth factor (Egf, a mitotic growth factor). We found that Ngf and Egf acted on the same IGR gene promotor element of the |-Srgap2-Fam72a-| master gene to mediate cell differentiation and proliferation, respectively. Ngf mediated Srgap2 expression and neuronal survival and differentiation while Egf activated Fam72a transcription and cell proliferation. Our data provide new insights into the specific regulation of the |-Srgap2-Fam72a-| master gene with its dual IGR promotor that controls two reverse-oriented functional-dependent 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.
This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), which was funded by the Ministry of Education (2015R1D1A1A01057243).
en
SPRINGER
Brain
Cell cycle
Differentiation
Divergent transcription
Gene promotor
Proliferation
A Novel Divergent Gene Transcription Paradigm-the Decisive, Brain-Specific, Neural |-Srgap2-Fam72a-| Master Gene Paradigm
Article
10.1007/s12035-019-1486-5
1-9
MOLECULAR NEUROBIOLOGY
Ho, Nguyen Thi Thanh
Kutzner, Arne
Heese, Klaus
2019000135
S
COLLEGE OF ENGINEERING[S]
DEPARTMENT OF INFORMATION SYSTEMS
kutzner
http://orcid.org/0000-0001-5061-6936