HOX-genes and MIR10A in ME

The genes HOXB3, HOXB4, HOXB5, HOXB-AS3 (LOC404266) and MIR10A are located together on chromosome 17.

MIR10A is hypermethylated, HOXB5 and LOC404266 are hypomethylated in CD4⁺ T-cells from ME patients (1).

The HOXB4 gene promoter is hypomethylated in peripheral blood mononuclear cells (PBMC) from ME patients (table S7 in ref 2).

HOXB3 (5'UTR), HOXB4 (1stExon, 5'UTR), LOC404266, HOXB5 (5'UTR), LOC404266 (TSS200, TSS1500) and MIR10A (1stExon, TSS1500) are hypomethylated in PBMC from ME patients (table S4 in ref 2).

HOXB3 (5'UTR), HOXB4 (body), HOXB5 (3'UTR), LOC404266 (TSS200, TSS1500, body) and MIR10A (TSS1500) are hypermethylated in PBMC from ME patients (table S7 in ref 3).

HOXB3, HOXB4, LOC404266 and MIR10A are differentially methylated in ME subtypes (table S3 in ref 4).

Why are HOX-genes hypomethylated in Trivedi's study and hypermethylated in de Vega's study?

DNA methyltransferase DNMT3A and DNMT3B are responsible for de novo methylation, while DNMT1 is responsible for maintaining methylation signatures.

DNMT3A (TSS1500) is hypomethylated in the Trivedi study (table S4 in ref 2).

DNMT3A (body) and DNMT3B (5'UTR) are hypermethylated in the de Vega (2017) study (table S7 in ref 3).

DNMT3A (body) and DNMT3B (5'UTR) are differentially methylated in ME subtypes (table S3 in ref 4).

References:

1. Brenu et al: Methylation profile of CD4+ T cells in CFS/ME. J. Clin Cell Immunol 5, 228  
2. Trivedi et al: Identification of ME/CFS - associated DNA methylation patterns. Plos One 2018, 13, 7 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0201066
3. de Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324230/
4. de Vega et al: Integration of DNA methylation & health scores identifies subtypes in ME/CFS. Epigenomics 2018, 10, 5 https://www.futuremedicine.com/doi/full/10.2217/epi-2017-0150