Histone code hypothesis

A significant portion of the histone variability described in the previous sections affects the electrostatic charge or hydrophobic character of these proteins particularly at the N- and C-terminal regions of the molecule. While some of these modifications appear to be used as a coding mechanism [121,123,165] (see histone code hypothesis, Fig. 5), the changes in the polarity also most likely play an additionally important role in the modulation of the histone-DNA... 

He, S. et al. (2003) Facile synthesis of site-specifically acetylated and methylated histone proteins reagents for evaluation of ihe histone code hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 100, 12033-12038. 

In cells of the mammary gland, either in normal epithelial or in cancerous cells, the packaging of chromosomal DNA into chromatin restricts the access of the transcription machinery, thereby causing transcriptional repression. The basic N-termini of histones are subject to post-translational modifications, including lysine acetylation, lysine and arginine methylation, serine phosphorylation and ubiquitinylation [56]. It has been proposed in the histone code hypothesis that the intricate pattern of modifications of the N-terminal histone tail influences gene regulation [57]. 

In contrast to simple charge neutralization effects, the effects on protein recog-nition/recruitment are collectively referred to as the histone code . This hypothesis predicts that specific patterns of histone tail acetylations and other modifications serve as epigenetic marks for distinct sets of regulatory proteins to differentially modulate chromatin structure and function (Strahl and Allis, 2000 Turner, 2000 Jenuwein and Allis, 2001). Indeed, several recent findings have demonstrated that histone acetylation creates a signal for the binding of a bromodomain which has... 

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