Pericentromeric concentration of transcription factors by junk DNA

The distributions of many transcription factors are not uniform throughout the cell nucleus. We have observed that the distribution of CCAAT/Enhancer Binding Protein alpha (C/EBPα) varies in different cell types. We also established that the binding of C/EBPα to mouse major α‐satellite repetitive DNA sequesters C/EBPα in pericentromeric heterochromatin. This reduces the ability of C/EBPα to activate non‐pericentromeric genes. However, the visible concentration of C/EBPα in the cell nucleus, due to binding to α‐satellite DNA, leads to the hypothesis that such junk DNA binding enhances C/EBPα access to genes immediately adjacent to the repetitive DNA. Indeed, fluorescence recovery after photobleaching experiments showed that C/EBPα associates dynamically with the pericentromeric heterochromatin thereby leading to a higher concentration in the adjacent nuclear subcompartment. Furthermore, a preliminary genome‐wide survey of C/EBPα‐regulated genes showed a higher extent of activation of C/EBPα in the immediate neighborhood of the α‐satellite DNA and we are now establishing whether this is true for other transcription factors in other cell types. Together with our findings that there are cell‐specific differences in the ability of C/EBPα to bind α‐satellite DNA and to concentrate at pericentromeric heterochromatin, a new paradigm in transcriptional regulation is emerging in which the same, differentially distributed transcription factor will regulate the transcription of a different cohort of genes in different cell types.