TRRAP-mediated acetylation on Sp1 regulates adult neurogenesis.

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.

HAT cofactor TRRAP modulates microtubule dynamics via SP1 signaling to prevent neurodegeneration.

Brain homeostasis is regulated by the viability and functionality of neurons. HAT (histone acetyltransferase) and HDAC (histone deacetylase) inhibitors have been applied to treat neurological deficits in humans; yet, the epigenetic regulation in neurodegeneration remains elusive. Mutations of HAT cofactor TRRAP (transformation/transcription domain-associated protein) cause human neuropathies, including psychosis, intellectual disability, autism, and epilepsy, with unknown mechanism.

Kinetics of poly(ADP-ribosyl)ation, but not PARP1 itself, determines the cell fate in response to DNA damage in vitro and in vivo.

One of the fastest cellular responses to genotoxic stress is the formation of poly(ADP-ribose) polymers (PAR) by poly(ADP-ribose)polymerase 1 (PARP1, or ARTD1). PARP1 and its enzymatic product PAR regulate diverse biological processes, such as DNA repair, chromatin remodeling, transcription and cell death. However, the inter-dependent function of the PARP1 protein and its enzymatic activity clouds the mechanism underlying the biological response.