Background: DNA methylation can regulate gene expression by recruiting or restricting the access of transcription factors. Global genomic studies have revealed that DNA methylation changes both at CpG islands and non CpG island regions during erythroid development and differentiation. Chromatin occupancy data indicate that many transcription factors involved in erythropoiesis contain CpG within their core consensus DNA binding motifs. We hypothesized that methylation of the CpGs within these binding motifs might directly influence erythropoiesis related transcription factor binding and gene regulation.

Results: Using in vitro assays we revealed that DNA methylation can either positively or negatively affect binding of important erythroid transcription factors to their DNA target sites. Based on these in vitro results, we analyzed ChIP-Seq and genome-wide bisulfite sequencing datasets to find target genes of key erythroid transcription factors in vivo where DNA methylation status changes during erythroid differentiation. We are now validating these in vivo target genes to uncover how target site methylation modulates the genetic regulation during erythroid differentiation.

Conclusion: We have shown that DNA methylation at transcription factor binding sites influences the binding affinity of key erythroid transcription factors in vitro and are extending these finding to in vivo target genes. Our study will improve the understanding of the relationship between DNA methylation, transcription factor binding and gene regulation in erythropoiesis.