Pioneer factors can also affect transcription and differentiation through the control of DNA methylation.  Pioneer factors that bind to CpG islands and cytosine residues block access to methyltransferases.  Many eukaryotic cells have CpG islands in their promoters that can be modified by methylation having adverse effects on their ability to control transcription.  This phenomenon is also present in promoters without CpG islands where single cytosine residues are protected from methylation until further cell differentiation.  An example is FoxD3 preventing methylation of a cytosine residue in Alb1 enhancer, acting as a place holder for FoxA1 later in hepatic   as well as in CpG islands of genes in chronic lymphocytic leukemia.  For stable control of methylation state the cytosine residues are covered during mitosis, unlike most other transcription factors, to prevent methylation.  Studies have shown that during mitosis 15% of all interphase FoxA1 binding sites were bound.  The protection of cytosine methylation can be quickly removed allowing for rapid induction when a signal is present.