ABSTRACT
TGS is the result of histone modifications, creating an environment of heterochromatin around a gene that makes it inaccessible to transcriptional machinery (RNA polymerase, transcription factors, etc.). The primary cause of TGS is thought to be cytosine methylation, in 5-CG-3 sequences of eukaryotic DNA, of promoter sequences, but the exact role of promoter methylation in TGS remains unclear. Occasionally, 5’-CNG-3’ sequences are also methylated. Methylation presumably inactivates the promoter by blocking its proper interactions with transcription factors
or by attracting chromatin-remodeling proteins, which could lead to the heterochromatinization of the promoter sequence. The methyl groups project into the major groove of the DNA and thus hinder the binding of most transcription factors. In addition, methylated CG sequences are recognized by methylcytosine binding proteins (MeCPs). Bound MeCPs are, in turn, recognized by other proteins that remove acetyl groups from the histones (especially H4). This results in the condensation of the DNA to form heterochromatin that is no longer accessible for transcription. The genes in such regions are said to be “silenced” (Clark 2005, Wang and Waterhouse 2002, Khan 2007).
