High throughput bisulfite sequencing of the MLH1 promoter in human hematiopoietic progenitor cell clones

Using single molecule ultra-deep bisulfite sequencing we characterized the CpG methylation landscape from –938 to –337 bp upstream of the MLH1 transcriptional start site position 0, from 30 hematopoietic colony forming cell clones (CFC) either expressing or not expressing MLH1. We identify a correlation between MLH1 promoter methylation and loss of MLH1 expression. Additionally, using the CpG site methylation frequencies obtained in this study we are able to generate a classification algorithm capable of sorting the expressing and non-expressing CFC. Thus, as previously described for many tumor cell types, MLH1 promoter methylation in hematopoietic stem cell clones correlates with the loss of MLH1 expression, a critically important gene in the mismatch repair pathway.