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1000
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Abstract/Summary
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The adult hippocampal neurogenesis plays a vital role in the function of the central nervous system (CNS), including memory consolidation, cognitive flexibility, emotional function, and social behavior. The deficiency of adult neural stem cells (aNSCs) in maintaining the quiescence and entering cell cycle, self-renewal and differentiation capacity is detrimental to the functional integrity of neurons and cognition of the adult brain. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) have been shown to modulate brain functionality and are important for embryonic neurogenesis via regulation of gene transcription. We showed previously that Trrap, an adapter for several HAT complexes, is required for Sp1 transcriptional control of the microtubule dynamics in neuronal cells. Here, we find that Trrap deletion compromises self-renewal and differentiation of aNSCs in mice and in cultures. We find that the acetylation status of lysine residues K16, K19, K703 and K639 all fail to overcome Trrap-deficiency-incurred instability of Sp1, indicating a scaffold role of Trrap. Interestingly, the deacetylation of Sp1 at K639 and K703 greatly increases Sp1 binding to the promoter of target genes, which antagonizes Trrap binding, and thereby elevates Sp1 activity. However, only deacetylated K639 is refractory to Trrap deficiency and corrects the differentiation defects of Trrap-deleted aNSCs. We demonstrate that the acetylation pattern at K639 by HATs dictates the role of Sp1 in the regulation of adult neurogenesis.
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