Chromatin modifiers

Like HATs, most functional HDACs are embedded in large multifunctional protein complexes, which also contain other chromatin modifying enzymes and coregulator proteins [1]. 

In the case of liganded NRs, ligand binding is the first and ciucial molecular event that switches the function of these transcription factors from inactive to active state by inducing a conformational change in the LBD of the receptor (Fig. 1). This specific conformation allows the second step of NR activation that corresponds to the recruitment of coregulatoiy complexes, which contain chromatin-modifying enzymes required for transcription. The transcriptional coactivators are very diverse and have expanded to more than hundred in number. These include the pi 60 family of proteins,... 

Another large family of coregulator proteins remodel chromatin, modify other transcription factots, and bridge the nuclear receptors to the basal ttanscription apparatus. 

Marban C, Suzanne S, Dequiedt F, de Walque S, Redel L, Van Lint C, Aunis D, Rohr O (2007) Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J 26(2) 412-423... 

Santos-rosa H, Caldas C (2005) Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 41 2381-2402... 

Downs JA, Allard S, Jobin-Robitaille O, Javaheri A, Auger A, Bouchard N, Kron SJ, Jackson SP, Cote J (2004) Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites. Mol Cell 16 979-990... 

Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M (2001) Activation of AMLl -mediated transcription by MOZ and inhibition by the MOZ-CBP hsion protein. EMBO J 20 7184-7196 Klochendler-Yeivin A, Yaniv M (2001) Chromatin modifiers and tumor suppression. Biochim Biophys Acta 155LMI-10... 

Hassan AH, Prochasson P, Neely KE, Galasinski SC, Chandy M, Carrozza MJ, Workman JL (2002) Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Cell 111 369-379... 

Chromatin-modifying complexes are classified into two major groups (1) enzymes that conttol covalent modifications of the amino-terminal tails of histones (acetylation, methylation, phosphorylation, ubiquitinylation) (see Sections 1.3 and... 

In eukaryotic ceDs, DNA is packaged in chromatin structures, and gene expressioii typically requires activation to occur. Chromatin-modifying activities include ... 

Recruit chromatin-modifying proteins such as histone acetylases or deacetylases... 

Local chromatin-modifying activities Acetylation of histones increases gene expression (many genes) Methylation of DNA silences genes in genetic imprinting (Prader-Willi and Angelman syndromes)... 

Kornberg, R.D. and Lorch, Y. (1999) Chromatin-modifying and -remodeling complexes. Curr. Opin. Genet. Dev. 9, 148-151. 

Tran, H.G., Steger, D.J., Iyer, V.R., and Johnson, A.D. (2000) The chromo domain protein Chdlp from budding yeast is an ATP-dependent chromatin-modifying factor. EMBO J. 19, 2323-2331. 

Mai, A. (2007) The therapeutic uses of chromatin-modifying agents. Expert Opinion on Therapeutic Targets,... 

So far nine arginine methyltransferases [46] and more than 20 lysine methyltransferases [11] have been identified in humans. Many of them show links to cancer. We discuss several of these subtypes below and an overview can be found in Tables 12.1 and 12.2. For lysine methyltransferases traditionally individual names have been used for the various subtypes. Lately, a common nomenclature for chromatin modifying enzymes has been proposed. For the human lysine methyltransferases the name KMTs should be used in analogy to (P)RMTs and eight groups (KMTl-8) with different subtypes suggested for some members [47]. But this nomenclature is not used consistently even throughout the recent literature so we provide both names if available in Table 12.2. 

The amount of information is still insufficient to predict how packaging of DNA in chromatin modifies the final product distribution in DNA. If the stable end products reflect a doubling in reductive damage while oxidative damage remains the same, then one would expect an increase in frequency and complexity of clustered lesions. If that proves true, the histone proteins and attending nucleosomes structure would act as radiation sensitizers. 

Kadonaga, J.T. Eukaryotic transcription an interlaced network of transcription factors and chromatin-modifying machines (1998) Cell 92, 307-13. 

Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in GO cells. Science 2002 296 1132-1136. 

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