CBX3 (HP1gamma) and the polycomb group (PcG) repressor complex PRC1.6 associate with the E2F6.com-1 complex. The PRC1.6 complex shown to associate with E2F6 consists of PCGF6 (MBLR), RING1 (RING1A) or RNF2 (RING2, also known as RING1B), YAF2 and L3MBTL2. The E2F6.com-1 complex is composed of E2F6, TFDP1 (DP-1), MGA, MAX, EHMT1 (GLP) and EHMT2 (G9a). This complex likely has a histone H3 methyltransferase activity and may be involved in creating the repressive H3K9Me mark at target genes, which would result in transcriptional repression (Ogawa et al. 2002).
As inferred from mouse, CBX3 (Heterochromatic Protein 1gamma, HP1gamma) binds histone H3 dimethylated at lysine-9 (H3K9me2). In other regions of the genome, CBX3 can be associated with repression of transcription, however dimethylated H3 lysine-9 and CBX3 in the transcribed region of the rRNA gene are associated with enhanced expression. CBX3 bound to gene bodies can facilitate cotranscriptional processing of RNA (Smallwood et al. 2012).
The E2F6.com-1 complex, consisting of transcription factors E2F6, TFDP1 (DP 1), MGA, MAX, histone methyltransferases EHMT1 (GLP) and EHMT2 (G9a), in complex with CBX3 (HP1gamma) and likely PRC1.6, binds to the E2F1 gene promoter. Presence of PRC1.6 components at the E2F1 gene promoter has not been tested, but is assumed based on association of PRC1.6-interacting protein CBX3 with the E2F1 promoter and the joint binding of CBX3 and PRC1.6 to the E2F6.com-1 complex (Ogawa et al. 2002). Besides the E2F1 gene promoter, the complex of E2F6.com-1 with CBX3 and possibly PRC1.6 was shown to bind to promoters of other genes involved in cell cycle progression, namely MYC, CDC25A and TK1 (Ogawa et al. 2002). However, transcriptional regulation of MYC, CDC25A and TK1 by E2F6 has not been directly demonstrated, and therefore association of E2F6 with these gene loci is not shown.
The PRC1L4 complex, consisting of E2F6, CBX3 (HP1gamma), PCGF6 (MBLR), L3MBTL2, and RING1 (RING1A) or RNF2 (RING2, also known as RING1B), binds the promoter of the CDC7 gene (Trojer et al. 2011).
E2F6 forms a complex with CBX3 (HP1gamma) and components of the polycomb repressor complex PRC1.6: PCGF6 (MBLR), L3MBTL2, RING1 (RING1A) or RNF2 (RING2, also known as RING2B). This polycomb repressor-like complex is named PRC1L4. Unlike the complex composed of E2F6.com-1, PRC1.6 and CBX3 (Ogawa et al. 2002), the PRC1L4 complex does not possess histone methyltransferase activity. Instead, the PRC1L4 complex may have a histone E3-ubiquitin ligase activity. The PRC1L4 complex was shown to bind to promoters of several genes: CDC7, CSTF3, MCM3, UXT, RPA2, RAD51C, RFC3, HOXC5. Of these genes, transcriptional repression was tested and demonstrated for CDC7 and UXT (Trojer et al. 2011).
About half of the rRNA genes in the genome are actively expressed, being transcribed by RNA polymerase I (reviewed in Nemeth and Langst 2008, Bartova et al. 2010, Goodfellow and Zomerdijk 2012, Grummt and Langst 2013). As inferred from mouse, those genes that are expressed are activated by ERCC6 (also known as Cockayne Syndrome protein, CSB) which interacts with TTF-I bound to the T0 terminator region (also know as the Sal Box) of rRNA genes (Yuan et al. 2007, reviewed in Birch and Zomerdijk 2008, Grummt and Langst 2013). ERCC6 recruits the histone methyltransferase EHMT2 (also known as G9a) which dimethylates histone H3 at lysine-9 in the coding region of rRNA genes. The dimethylated lysine is bound by CBX3 (also known as Heterochromatic Protein-1gamma, HP1gamma) and increases expression of the rRNA gene. Continuing dimethylation depends on continuing transcription. Mutations in CSB result in dysregulation of RNA polymerase I transcription, which plays a role in the symptoms of Cockayne Syndrome (reviewed in Hannan et al. 2013).