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Neurobiol Learn Mem. 2011 Jul;96(1):27-34. doi: 10.1016/j.nlm.2011.04.002. Epub 2011 Apr 16.

HDAC3 and the molecular brake pad hypothesis.

Author information

1
University of California, Irvine, Department of Neurobiology and Behavior, Center for the Neurobiology of Learning and Memory, Institute for Memory Impairments and Neurological Disorders, United States.

Abstract

Successful transcription of specific genes required for long-term memory processes involves the orchestrated effort of not only transcription factors, but also very specific enzymatic protein complexes that modify chromatin structure. Chromatin modification has been identified as a pivotal molecular mechanism underlying certain forms of synaptic plasticity and memory. The best-studied form of chromatin modification in the learning and memory field is histone acetylation, which is regulated by histone acetyltransferases and histone deacetylases (HDACs). HDAC inhibitors have been shown to strongly enhance long-term memory processes, and recent work has aimed to identify contributions of individual HDACs. In this review, we focus on HDAC3 and discuss its recently defined role as a negative regulator of long-term memory formation. HDAC3 is part of a corepressor complex and has direct interactions with Class II HDACs that may be important for its molecular and behavioral consequences. And last, we propose the "molecular brake pad" hypothesis of HDAC function. The HDACs and associated corepressor complexes may function in neurons, in part, as "molecular brake pads." HDACs are localized to promoters of active genes and act as a persistent clamp that requires strong activity-dependent signaling to temporarily release these complexes (or brake pads) to activate gene expression required for long-term memory formation. Thus, HDAC inhibition removes the "molecular brake pads" constraining the processes necessary for long-term memory and results in strong, persistent memory formation.

PMID:
21521655
PMCID:
PMC3111848
DOI:
10.1016/j.nlm.2011.04.005
[Indexed for MEDLINE]
Free PMC Article

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