Tip off the HAT- Epigenetic control of learning and memory by Drosophila Tip60

Fly
Songjun Xu, Felice Elefant

Abstract

Disruption of epigenetic gene control mechanisms involving histone acetylation in the brain causes cognitive impairment, a debilitating hallmark of most neurodegenerative disorders. Histone acetylation regulates cognitive gene expression via chromatin packaging control in neurons. Unfortunately, the histone acetyltransferases (HATs) that generate such neural epigenetic signatures and their mechanisms of action remain unclear. Our recent findings provide insight into this question by demonstrating that Tip60 HAT action is critical for morphology and function of the mushroom body (MB), the learning and memory center in the Drosophila brain. We show that Tip60 is robustly produced in MB Kenyon cells and extending axonal lobes and that targeted MB Tip60 HAT loss results in axonal outgrowth disruption. Functional consequences of loss and gain of Tip60 HAT levels in the MB are evidenced by defects in memory. Tip60 ChIP-Seq analysis reveals enrichment for genes that function in cognitive processes and accordingly, key genes representing these pathways are misregulated in the Tip60 HAT mutant fly brain. Remarkably, increasing levels of Tip60 in the MB rescues learning and memory deficits resulting from Alzheimer's disease associated am...Continue Reading

References

Aug 15, 1993·The Journal of Comparative Neurology·J Rybak, R Menzel
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·A FossgreenR Paro
Jun 6, 2000·Microbiology and Molecular Biology Reviews : MMBR·D E Sterner, S L Berger
Apr 13, 2001·Current Biology : CB·J Dubnau, T Tully
Jun 8, 2001·Annual Review of Biochemistry·S Y RothC D Allis
Feb 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emma HocklyGillian P Bates
Mar 19, 2003·Journal of Neurochemistry·Sangeeta ChawlaHilmar Bading
Apr 3, 2003·Nature Reviews. Neuroscience·Martin Heisenberg
Aug 19, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hye-Sun KimYoo-Hun Suh
Oct 15, 2003·Behavioural Processes·Kathleen K. Siwicki, Lisa Ladewski
Dec 6, 2003·The EMBO Journal·Caroline RouauxAnne-Laurence Boutillier
Mar 27, 2004·The Journal of Biological Chemistry·Xinwei Cao, Thomas C Südhof
Apr 16, 2004·Current Biology : CB·Ryan J WattsLiqun Luo
Oct 21, 2004·The Journal of Biological Chemistry·Gabriella GardianM Flint Beal
Dec 8, 2004·Current Opinion in Neurobiology·Jennifer E MehrenLeslie C Griffith
Jan 18, 2005·Nature Reviews. Neuroscience·Jonathan M Levenson, J David Sweatt
Aug 17, 2005·The Journal of Biological Chemistry·Matthew R Hass, Bruce A Yankner
Sep 6, 2005·Current Biology : CB·Carla MarguliesJosh Dubnau
Jul 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·R W Siegel, J C Hall
Sep 19, 2006·Learning & Memory·David-Benjamin G AkalalRonald L Davis
Nov 10, 2006·Molecular Biology of the Cell·Thorsten MüllerRupert Egensperger
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Bin LiMark I Greene
Apr 7, 2007·Pediatric Research·Jian FengGuoping Fan
Apr 25, 2007·Nature Reviews. Neuroscience·Alex C Keene, Scott Waddell
May 25, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Caroline RouauxJean-Philippe Loeffler
Jun 26, 2007·Science·Tiago Fleming OuteiroAleksey G Kazantsev
Feb 5, 2008·Current Opinion in Neurobiology·André Fiala
Oct 2, 2008·Nature Reviews. Drug Discovery·Aleksey G Kazantsev, Leslie M Thompson
Dec 27, 2008·Neuron·Emiliana BorrelliPaolo Sassone-Corsi
Oct 20, 2009·Neuroscience Letters·Yong WangXiaomin Wang
Oct 20, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kaushik GhosalSanjay W Pimplikar
Apr 16, 2010·Nature·Tae-Kyung KimMichael E Greenberg
May 8, 2010·Science·J David Sweatt
May 11, 2010·Current Opinion in Neurobiology·Tamara B Franklin, Isabelle M Mansuy
Sep 9, 2010·Essays in Biochemistry·Tania L RothJ David Sweatt

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Methods Mentioned

BETA
acetylation
histone acetylation
transgenic
dissection
ChIP-Seq

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