Histone classic

De ruijter AJM, Vangennip AH, Caron HN, Kemp S, Vankuilenburg ABP (2003) Histone deacety-lases (hdacs) characterization of the classical hdac family. Biochem J 370 737-749... 

Daujat S, Bauer UM, Shah V, Turner B, Berger S, Kouzarides T (2002) Crosstalk between CARMl methylation and CBP acetylation on histone H3. Curr Biol 12 2090-2097 de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs) characterization of the classical HDAC family. Biochem J 370 737-749 Decker J, Struhl K (2001) Histone acetylation at promoters is differentially affected by specific activators and repressors. Mol Cell Biol 21 2726-2735... 

Fig. 8. The classical histone handshake motif shown in a ribbon Ca model of the interdigitating H3 H4 heterodimer. Additional stabilization of the heterodimeric structure is provided by the formation of a short parallel /J-bridge between the C-terminal loop occurring after the medial helix of H3 and the N-terminal loop occurring before the medial helix of H4. This /i-bridge provides a platform for DNA binding.

Figure 2.3 Structures of mammalian classic histone deacetylases. Ribbon representation of the conserved catalytic domain of (a) class I human HDAC8 in complex with trichostatin A (TSA PDB code lt64), (b) human HDAC8 Tyr306Phe inactive mutant in complex with a peptidic acetyl-lysine substrate (PDB code 2v5w), (c) class I la human...

It should be noted that HATs and HDACs are not only limited to histones, but rather various nonhistone proteins can be acetylated/deacetylated as well [2, 4]. Many regulators of DNA repair, recombination and replication, viral proteins, classic metabolic enzymes (e.g. bacterial and mammalian acetyl-CoA synthases) and... 

The role of histone becomes, thus, part of the problem of how the environment affects gene activity. Biology has by now outgrown the abstract and rigid limitations of classical genetics for now it is dear that the chromosome, like other centres of vital activity, is subject to regulation by feed-back of the periphery. A. E. Mirsky, 1965 (sic ) [1]... 

HDACs are zinc metalloproteases involved in the acetylation of histone. Inhibition of HDACs represents a new strategy in human cancer therapy since these enzymes play a fundamental role in regulating gene expression and chromatin assembly. Along this line, inhibition of HD AC by fluoroketones has been studied. The inhibition power of fluoroketones toward HDACs is comparable to that of hydroxamates, which are the classical inhibitors of metalloproteases. These fluoroketones exhibit antiproliferative activities on tumor cell lines (Figure 7.44). ... 

Figure 2.1 Schematic, simplified representation of the modulation of nuclear receptor functioning via classical agonists (a) resulting in the recruitment of coactivators featuring among others histone acetyltransferase (HATs) functionalities and via classical antagonists (b) resulting in the recruitment of corepressors...

Stable forces are also obtained in MM/PCM simulations, as shown in Fig. 11.9 for a classical MD simulation of a segment of DNA bound to a histone protein. Here, the energy fluctuations amount to an acceptable 0.0001% of the total energy. 

Histone deacetylases (HDACs, EC number 3.5.1) remove acetyl groups from A -acetyl lysines by hydrolysis, both on histones and non-histone proteins, hence are more generally referred to as lysine deacetylases (KDACs). HDACs are grouped into four classes based on sequence homology and mechanism (Table 5.2). The first two classes, sometimes referred to as classical HDACs, are zinc-dependent and their activity is inhibited by hydroxamic acids, e.g. trichostatin A (TSA). The third class, referred to as Sirtuins, are NAD -dependent proteins and are not inhibited by TSA. The fourth class is also zinc-dependent, but is considered an atypical category based on low sequence homology to classes I and II. Class I and IV HDACs are mainly found in the nucleus and are expressed in many cell types, while the expression of class II HDACs, which are able to shuttle in and out of the nucleus, is tissue specific. Sirtuin localisation depends on the particular isoform (cytoplasm, mitochondria and nucleus). 

All types of histones are found in chromatin in equi-molecular amounts except for FI of which there is only half as much as of the other histones. We have seen that in the classical view, based on X-ray crystallography studies, the DNA histone complexes in chromatin are believed to form a supercoiled helical structure. Although it is certain that chromatin fibers are... 

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