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Intracellular Trafficking of Histone Deacetylase 4 Regulates Long‐Term Memory Formation
Author(s) -
Wang WenHan,
Cheng LiCheng,
Pan FeiYan,
Xue Bin,
Wang DaYong,
Chen Zhong,
Li ChaoJun
Publication year - 2011
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.21389
Subject(s) - hdac4 , histone , caenorhabditis elegans , biology , microbiology and biotechnology , histone deacetylase , mutant , wild type , acetylation , hdac11 , histone deacetylase 5 , hdac6 , histone acetyltransferase , phenotype , hdac10 , hdac1 , genetics , gene
Histone acetylation is important for gene transcription, which is controlled by the balance between two kinds of opposing enzymes: histone acetyltransferases and histone deacetylases (HDACs). HDACs repress gene transcription by decreasing histone acetylation levels. Our hypothesis was that shuttling of Class II HDACs, such as HDAC4, between the nucleus and cytoplasm is critical for its function. We constructed mutants of mammalian HDAC4 that had different cellular locations and checked their function during memory formation using Caenorhabditis elegans as a model. The deletion of hda4 , a homolog of HDAC4 , was able to enhance learning and long‐term memory (LTM) in a thermotaxis model. Transgenic experiments showed that mammalian wild‐type HDAC4 rescued the phenotype of hda4 ‐deleted worms but impaired LTM formation in wild‐type worms. The cytosol‐localized HDAC4 mutant was not able to alter the phenotype of knock‐out worms but led to enhanced LTM formation in wild‐type worms similar to hda4 ‐deletion mutants. Constitutive nuclear localization of HDAC4 rescued the phenotype of deletion worms similar to wild‐type HDAC4 but had no effect on wild‐type worms. These results support our hypothesis that HDAC4′s biological function is regulated by its intracellular distribution. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.