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Neuronal differentiation alters the ratio of Sp transcription factors recruited to the CYP46A1 promoter
Author(s) -
Milagre Inês,
Nunes Maria João,
CastroCaldas Margarida,
Moutinho Miguel,
Gama Maria João,
Rodrigues Elsa
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07577.x
Subject(s) - sp1 transcription factor , promoter , biology , transcription factor , receptor , glutamate receptor , gene expression , gene , protein subunit , microbiology and biotechnology , biochemistry
J. Neurochem. (2012) 120 , 220–229. Abstract CYP46A1 is a neuron‐specific cytochrome P450 that plays a pivotal role in maintaining cholesterol homeostasis in the CNS. However, the molecular mechanisms underlying human CYP46A1 expression are still poorly understood, partly because of the lack of a cellular model that expresses high levels of CYP46A1. Our previous studies demonstrated that specificity protein (Sp) transcription factors control CYP46A1 expression, and are probably responsible for cell‐type specificity. Herein, we have differentiated Ntera2/cloneD1 cells into post‐mitotic neurons and identified for the first time a human cell model that expresses high levels of CYP46A1 mRNA. Our results show a decrease in Sp1 protein levels, concomitant with the increase in CYP46A1 mRNA levels. This decrease was correlated with changes in the ratio of Sp proteins associated to the CYP46A1 proximal promoter. To examine if the increase in (Sp3 + Sp4)/Sp1 ratio was observed in other Sp‐regulated promoters, we have selected four genes ‐ reelin, glutamate receptor subunit zeta‐1, glutamate receptor subunit epsilon‐1 and μ‐opioid receptor ‐ known to be expressed in the human brain and analyzed the Sp proteins binding pattern to the promoter of these genes, in undifferentiated and differentiated Ntera2/cloneD1. Our data indicate that the dissociation of Sp1 from promoter regions is a common feature amongst Sp‐regulated genes that are up‐regulated after neuronal differentiation.