Role of polycomb repressive complex 2 in regulation of human transcription factor gene expression

The study described here was pursued with the idea that information about control of human gene expression might result from comparing the promoter regions of a highly expressed gene population with that of a related population that is weakly expressed. Systematic differences in the two promoter populations would be candidates for a role in causing the distinct expression levels observed. The results reported here were obtained with human genes encoding transcription factors (TF). Among TF genes, those with wide tissue transcription are strongly expressed while those expressed in one or only a few tissues are weakly transcribed in most cases. The promoter regions of the two populations were compared using the results of ChIP-seq experiments. Results demonstrated that the promoter region of broadly expressed TF genes is enriched in binding sites for POLR2A, a component of RNA polymerase II while promoters of tissue targeted genes are enriched in EZH2, a subunit of polycomb repressive complex 2 (PRC2). It was rare to observe promoters with binding sites for both POLR2A and EZH2 or for neither one. The findings are interpreted to indicate that strong expression of broadly expressed TF genes is due to the presence of RNA polymerase II at the promoter while weak expression of tissue targeted promoters results from the presence of PRC2. Finally, transcription factor families were compared in the proportion of broadly expressed and tissue targeted genes. The results demonstrated that most families possess both broadly expressed and tissue targeted members. For instance, this was the case with 16 of 20 TF families. The results are interpreted to indicate that while individual TFs such as EZH2 may be specific for broadly expressed or tissue targeted genes, this is not a property of most TF families. Most have both broadly expressed and tissue targeted members.