The secret message of heterochromatin: new insights into the mechanisms and function of centromeric and pericentric repeat sequence transcription

Abstract

In the fission yeast, S. Pombe, small dsRNA generated by RNAi-dependent mechanisms are involved in the establishment and maintenance of heterochromatic regions. The existence of conserved features within the general organization of centromeric and pericentromeric repeats in yeast, mouse and human argues in favor of a conserved role for centromeric and pericentromeric-derived transcripts across these species. In support of this, evidence is accumulating that centromeric and pericentromeric sequences are transcriptionally competent in diverse biological contexts in mammalian cells. Given the importance of centromeric and pericentromeric regions, not only with respect to centromere function, but also to gene regulation, this review examines the biological contexts in which mouse and human centromeric and pericentromericspecific transcripts have been observed. The structure of the transcripts generated, the molecular mechanisms underlying their expression and their supposed functions will be discussed.

Pericentric and centromeric transcription: a perfect balance required

“…From studies across major eukaryotic lineages, it is clear that PCTs have other roles in addition to heterochromatin formation and that some of these functions may be strand specific (Chen et al 2008;Eymery et al 2009a;Probst et al 2010). Recent research suggests that PCTs may play a role in the formation of chromocenters (Eymery et al 2009a;Probst et al 2010), nuclear structures formed from the aggregation of heterochromatin from multiple chromosomes.…”

“…Recent research suggests that PCTs may play a role in the formation of chromocenters (Eymery et al 2009a;Probst et al 2010), nuclear structures formed from the aggregation of heterochromatin from multiple chromosomes. The number of chromocenters present within a nucleus can be tissue specific and can change during cell differentiation (Ceccarelli et al 1998).…”

“…The number of chromocenters present within a nucleus can be tissue specific and can change during cell differentiation (Ceccarelli et al 1998). PCTs and centromeric transcripts or CTs are shown to localize to chromocenters as mouse cells differentiate into muscle cells (Eymery et al 2009a). Another study examining developing mouse embryos illustrates that major satellite PCTs are required for the formation of chromocenters at the two-cell stage of development (Probst et al 2010).…”

“…Differences in strand expression from the pericentromere are also observed in adult mouse tissues and human cells [reviewed in Eymery et al (2009a)]. For example, expression of the antisense strand of PCTs in mouse testis was found only to be present within seminiferous tubules lacking mature sperm (Rudert et al 1995).…”

“…The chromatin encompassing the centromere core, also referred to as "centrochromatin," is distinct from that of pericentromeres and contains the histone H3 variant CENP-A interspersed with histone H3 methylation and dimethylation of lysine 4 and di-and trimethylation of lysine 36 of histone H3 (H3K4me1, H3K4me2, H3K36me2, and H3K36me3), histone modifications associated with transcriptionally active chromatin (Sullivan and Karpen 2004;Gopalakrishnan et al 2009;Bergmann et al 2011Bergmann et al , 2012. Interestingly, transcripts emanating from both the pericentromere and centromere core have been identified in a multitude of organisms (Eymery et al 2009a;Stimpson and Sullivan 2010). Moreover, recent studies have identified proteins that interact with these transcripts (Topp et al 2004;Wong et al 2007;Chueh et al 2009;Ferri et al 2009;Du et al 2010;Hsieh et al 2011), analyzed the effects of increased and decreased transcription on genome stability (Bergmann et al 2011;Ohkuni and Kitagawa 2011;Bergmann et al 2012), or identified changes in transcription in stressed or diseased cells (Eymery et al 2009b;Gopalakrishnan et al 2009;Ting et al 2011;Zhu et al 2011).…”