Chromatin acetylation

Figure I. Chromatin acetylation status, transcription and survival a balance between HAT and HDAC activities, (a) Transcriptional activationlrepression relies on the chromatin acetylation status of histones. TBP TATA-Binding Protein, TF Transcription Factor, TR Transcriptional Repressor, (b) A fine-tuning of HAT/HDAC activities orchestrates neuronal death and survival. On one hand, acetylation levels can be decreased (HypoAc) because of CBP loss of function, as observed during apoptosis and neurodegeneration. On the other hand, when the threshold of acetylation is exceeded (HyperAc), this ultimately leads to nemonal death. (See Colom Plate 16.)...

HDAC9 is the predominant member of the class II HDAC family expressed in heart (Zhang et al, 2002). Its major product was shown to encode the splice variant MEF2-interacting transcription repressor/histone deacetylase-related protein (MITRIHDRP), which lacks the enzymatic domain but forms complexes with both HDACI and HDAC3 (Zhou et al, 2000 Zhou et al, 2001) and has been recently implicated in skeletal muscle chromatin acetylation and gene expression under motor innervation control (Mejat et al, 2005). 

Chromatin Acetylation Status During Neuronal Apoptosis... 

Alarcon JM, Malleret G, Touzani K, Vronskaya S, Ishii S, Kandel ER, Barco A (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/- mice a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42(6) 947-959 Alnernri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996) Human lCElCED-3 protease nomenclature. Cell 87(2) 171... 

McCampbell A, Taye AA, Whitty L, Penney E, Steffan JS, Fischbeck KH (2001) Histone deacetylase inhibitors reduce polyglutamine toxicity. Proc Natl Acad Sci U S A 98(26) 15179-15184 Mejat A, Ramond F, Bassel-Duby R, Khochbin S, Olson EN, Schaeffer L (2005) Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression. Nat Neurosci 8(3) 313-321... 

Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J (2006) ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell 21 51-64... 

Another function of H4 (SI) regulates chromatin acetylation by the NuA4 complex and this process is important for normal gene expression and DNA repair (Utley et al, 2005). 

MethDB, Human DNA Metbylation Database, http //www.methdb.de/. Reviews on chromatin acetylation. Oncogene 2007 26(37). Entire issue. 

Alarcon JM et al (2004) Chromatin acetylation, memory, and LTP are impaired in CBP+/— mice a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 42(6) 947-959... 

Acetylation and acylation. Acetylation of e-amino groups on conserved Lys residues in the N-terminal domains of the core histones, H2A, H2B, H3 and H4, is the most common post-translational modification of chromatin. Acetylation substantially weakens the constraints on DNA imposed by the core histones and provides molecular mechanism by which DNA becomes accessible to transacting factors while maintaining a nucleosome architecture (Wade et al, 1997). Histone acetylation is reversible and is controlled by a group of acetyltransferases and deacetylases. The balance between histone acetyltransferases and deacetylases determines the accessibility of the chromatin to the transcriptional machinery. Thus the acetylation status of histones is a key determinant of transcriptional activity. Transcription activators are often associated with histone acetyltransferases and repressors can interact with histone deacetylases (Ng and Bird, 2000). 

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