Transcription interference-mediated silencing by chromatin changes. (a) Top: in yeast the absence of SRG1 lncRNA allows transcription machinery assembly at the SER3 protein coding gene promoter. Bottom: SRG1 lncRNA transcription causes dense nucleosome packing over the downstream SER3 pc gene promoter that blocks TF binding and pc gene expression. (b) Top: in yeast the absence of IRT1 lncRNA allows IME1 pc gene expression. Bottom: RNAPII transcribing the IRT1 lncRNA carries EMs that deposit repressive histone modifications at the IME1 promoter (EM1 - methyltransferases). These modifications allow the binding of other EMs that remove active histone modifications (EM2 - deacetylases) and cause a repressive chromatin environment that blocks TF binding leading to silencing. (c) Top: in a healthy human, LUC7L and HBA2 pc genes do not overlap and are both expressed. Bottom: a chromosomal deletion of the LUC7L transcriptional stop signal (red ‘stop’ box) causes transcription of the LUC7L pc gene through the promoter of the HBA2 pc gene. By an unknown mechanism this aberrant transcription causes DNA methylation and silencing of the HBA2 promoter. For details see Figure 1g and text.