Fig. 7: Model for MSR-based instruction of de novo heterochromatin formation.
From: Transcriptional competence defines the heterochromatin nucleating potential of isolated MSR units
In this model, multi-copy units of the A/T-rich MSR DNA consensus sequence are intrinsically prone to form an altered topology that exposes single-stranded DNA and/or favours R-loop formation (indicated by the red and blue extensions). This partially unwound DNA template can serve as a promoter-mimic and facilitates RNA polymerase II (RNAPII) engagement, which is further guided by transcription factor (TF) binding to MSR DNA. MSR-derived transcription is bi-directional and attenuated by the RNAPII-associated Integrator (INT) complex. MSR transcripts (wavy dashed lines) have non-mRNA qualities and largely remain chromatin associated. MSR transcripts assist in the recruitment of HP1 and Suv39h enzymes and can stabilise an RNA-nucleosome scaffold. Heterochromatin establishment is matured by robust Suv39h-mediated H3K9me3 (Me), HP1 binding and histone H1 (H1) incorporation, which together form a more compact nucleosome structure and silence transcriptional activity. Abbreviations are: MSR (major satellite repeat), TF (transcription factor), Pol II (RNA polymerase II), INT (Integrator complex), Suv39h (H3K9 KMT), Me (H3K9me3), HP1 (heterochromatin protein 1), RNA (chromatin-associated MSR transcripts), H1 (histone H1). See text for detailed explanation.
