Although all the cells in an organism have the same genome, different tissues diverge in their gene expression profile and over time the same tissue will show different gene expression. This differences in gene expression patterns can be explained through epigenetics.
Chromatin modifications can affect a gene expression without modifications in the DNA sequence and can be responsible for the transition from euchromatin, more accessible chromatin with less condensed, to heterochromatin, a highly condensed state and transcriptionally silenced1.
It is known that heterochromatin has many different functions like in regulation of gene expression, chromosome segregation and genome stability2. The formation of this compacted structure is achieved by histone modification (acetylation, methylation) and is spreading through some complexes able to recruit some other proteins and in this way, mark the chromatin for condensation.
Usually for studies related with heterochromatin and the mechanisms behind heterochromatin assembly the fission yeast Schizosaccharomyces pombe is used as a model system due to its identity to some mammals’ proteins required for heterochromatin formation3 and because of its chromatin structure. The genome of the fission yeast has heterochromatin blocks in pericentromeric repeats, telomeres and in the mating-type region4 and heterochromatin formation in these regions involve some proteins that will lead to posttranslational histones modifications.
A hallmark of heterochromatin, essential for heterochromatin assembly and spreading, is the methylation of H3 lysine 9 (H3K9me). In fission yeast, H3K9 is mono-, di- and tri-methylated by the histone methyltransferase Clr4, homolog of Suv39 in mammals5. The mark H3K9me is, then, recognized by proteins like Swi6 and Chp2, chromodomain (CD) proteins homologs to the heterochromatin protein 1 (HP1) that bound to this mark and have a role in heterochromatin spreading by further methylation in adjacent histones6.
Another pathway involved in heterochromatin assembly and silencing is the RNA interference (RNAi) pathway and requires the intervention/recruitment of an RNAi complex called RITS (RNA-induced initiation of transcriptional gene silencing)4. Previously it was thought that heterochromatin was transcriptionally silenced, however new studies shown that this is not the case and there is still some transcription, even in low levels, in these loci5. However, through the RITS complex and interactions between the transcripts and RNAi, the transcripts originated from heterochromatin regions are degraded and therefore all the genes present in heterochromatin regions are fully silenced.
The RITS complex is composed of the Chp1, Tas3 and Ago1 proteins which one with different functions. The Chp1 protein is crucial for the establishment of the RITS complex because of its CD activity able to bound to the H3K9me.