Nucleoporins in ME

The nuclear pore complex (NPC) mediates nuclear transport of RNA. Nucleoporins are the main components of the NPC. Certain nucleoporins have additional function in chromatin organization and transcription regulation.

NUP98 and NUP96
The gene NUP98 encodes nucleoporin Nup98 and Nup96. They are expressed from one mRNA. Following translation, autoprotelytic cleavage separates the two proteins. Alternatively, Nup98 can be spliced as a short mRNA that does not encode Nup96 (1).

Interferon-induced gene promoters containing Nup98 accumulate poised RNA Pol II along with dimethylated histone H3K4 (1).

NUP98 recruits the Wdr82-Set1A/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells (2).

Nup98 associates with Trx/MLL and NSL Histone-modifying complexes and regulates Hox Gene expression (3).

Mice with low levels of Nup96 have impared interferon mediated induction of MHCI and II and altered T- and B-cell function (4).

NUP98 and HOXA1 are involved in the ME pathomechanism in severely ill ME patients (5).

Depletion of FOXK1 attenuates virus-inducible interferon-stimulated response element (ISRE) reporter expression. Drosophila FOXK interact with Nup98 to regulate antiviral gene expression (6).

FOXK1 is hypermethylated in ME patients in two studies (7, 8). The hypermethylation (3'UTR and body) is related to quality of life in ME patients (table S7 in ref 8).

FOXK1(body) is differentially methylated in ME subtypes (no 673 in table S3 in ref 9).

References

1. Franks et Hetzer: The role of Nup98 in transcription regulation in healty and diseased cells. Trends Cell Biol. 2013, 23, 3
2. Franks et al: Nup98 recruits the Wdr82-Set1a/COMPASS complex to promoters to regulate H3K4 trimethylation in hematopoietic progenitor cells. Genes Dev. 2017, 15, 31
3. Pascual-Garcia et al: Nucleporin Nup98 associates with Trx/MLL and NSL histone-modifying complexes and regulates HOX gene expression. Cell Rep. 2014, 9
4. Favia et al: The nucleoporin Nup96 is required for proper expression of interferon-regulated proteins and functions. Immunity 2006, 24
5. Pihur et al: Metaanalysis of CFS through integration of clinical, gene expression, SNP and proteomic data. Bioinformation 2011, 6, 3
6. Panda et al: The transcription factor FOXK participates with Nup98 to regulate antiviral gene expression. MBio, 2015, 7, 2
7. de Vega et al: DNA methylation Modifications associated with CFS. PlosOne, 2014, 9, 8
8. de Vega et al: Epigenetic modifications and glucocorticoid sensitivity in ME/CFS. BMC Medical Genomics, 2017, 10, 11
9. de Vega et al: Integration of DNA methylation & health scores identifies subtypes in ME/CFS. Epigenomics 2018, 10, 5