Bioruptor® in Action Video
Expertise | Chromatin function | The main histone modifications
The main histone modifications and their role in gene expression
Histone modifications are reversible changes in chromatin organisation that influence gene expression. When the chromatin is opened (or “active”), genes are expressed or are “on”. When the chromatin is condensed (or “silent”), genes are inactivated or are “off” (Rodenhiser and Mann 2006).
Histone acetylation (H3 and H4 at promoter regions) directly facilitates transcription by loosening histone-DNA contacts and is associated with recruitment of transcriptional activators containing an acetyl-lysine binding module: the bromodomain. Such bromodomains are motifs found in several eukaryotic transcription factors (Winston and Allis 1999).
Histone methylation correlates either with transcriptional repression or activation (Peterson and Laniel 2004, Brinkman et al. 2006, Allis et al. 2007). For instance, H3K27me3 correlates with transcription repression (at intergenic and silenced coding regions) but some histone methylation such as H3K4me3 (at promoter regions) correlates with transcription. It was shown that histone methylation of H3K9me3 is a silence mark, but it was also shown that it is enriched at coding regions of active genes (Brinkman et al. 2006).
Intergenic, coding, and promoter regions are segregated into differentially marked chromatin. Nevertheless, some new results show that individual marks are not exclusibe to heterochromatin or euchromatin, but rather suggest that composite patterns of interdependent or mutually exclusive modifications together signal the gene expression status (Brinkman et al. 2006). H3K27me3 is indeed most prominent in intergenic and silenced coding regions, but is associated with some active coding regions as well. Similarly, histone H3/H4 acetylation and H3K4me3 are locally enriched at promoter regions but do not necessarily mark continuing transcription (Brinkman et al. 2006). In addition, H3K9me3 was reported to be predominant in coding regions of active genes, a phenomenon that is not restricted to the X chromosome (Brinkman et al. 2006). Some methylated marks are interpreted through the recruitment of proteins containing chromodomains (Flanagan et al. 2005, Becker 2006).
The physical association of two enzymatic activities, histone methylation and histone deacetylation, which are thought to be involved in transcriptional silencing, provide the framework of a molecular model of how heterochromatin is initiated and maintained during cell division and differentiation (Czermin and Imhof 2003).
Six methylated histone sites have been well characterized: five on histone H3 (K4, K9, K27, K36 and K79) and one on H4 (H4K20) (see table below). Methylation at H3K4, H3K36 and H3K79 has been generally linked to activation of the transcription and the rest to repression. The table below shows some of the reported histone modifications and their link to transcription activation or repression. Note that in addition ubiquitylation can activate or repress the transcription (if at H2B or H2A, respectively) while sumoylation is repressing the transcription (Allis et al. 2007).
|Active marks||Silence marks|
|Acetylation||H3 (K9, K14, K18, K56)
H4 (K5, K8K12, K16)
H2B (K6, K7, K16, K17)
|Methylation||H3 (K9, K27)
|Methylation||H3(K4, K36, K79)|