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Publication : Class IIa HDACs regulate learning and memory through dynamic experience-dependent repression of transcription.

First Author  Zhu Y Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  3469
PubMed ID  31375688 Mgi Jnum  J:279488
Mgi Id  MGI:6362551 Doi  10.1038/s41467-019-11409-0
Citation  Zhu Y, et al. (2019) Class IIa HDACs regulate learning and memory through dynamic experience-dependent repression of transcription. Nat Commun 10(1):3469
abstractText  The formation of new memories requires transcription. However, the mechanisms that limit signaling of relevant gene programs in space and time for precision of information coding remain poorly understood. We found that, during learning, the cellular patterns of expression of early response genes (ERGs) are regulated by class IIa HDACs 4 and 5, transcriptional repressors that transiently enter neuronal nuclei from cytoplasm after sensory input. Mice lacking these repressors in the forebrain have abnormally broad experience-dependent expression of ERGs, altered synaptic architecture and function, elevated anxiety, and severely impaired memory. By acutely manipulating the nuclear activity of class IIa HDACs in behaving animals using a chemical-genetic technique, we further demonstrate that rapid induction of transcriptional programs is critical for memory acquisition but these programs may become dispensable when a stable memory is formed. These results provide new insights into the molecular basis of memory storage.
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