After differential regulatory network construction and TED scoring, we found that the interferon regulatory factor ( IRF ) family members, including IRF1, IRF3, IRF5, IRF7, and IRF9
, are important TFs in the early stage of DN.
In chronically activated T cells, IFN[alpha] causes prolonged PD1 transcription through the binding of activated IFN-stimulated gene factor 3 (ISGF3), a heterotrimer of STAT1 and STAT2 in association with IRF9
, to the PD1 promoter .
Type I IFN activates transcription of genes related to anti-microbial host defenses by acting through its receptor to induce nuclear translocation of a heterotrimeric complex, called IFN-stimulated gene factor 3 (ISGF3), the latter composed of signal transduction and activator of transcription 1 (Stat1), Stat2, and IRF9
. (65) Thus, in further studies relating NOD1 induction of type I IFN-induced responses to chemokine production Watanabe et al.
This enables complex formation with IRF9
to build the trimeric transcription factor ISGF3 which binds to the IFN-stimulated response element (ISRE), present in the upstream region of ISGs.
This process drives the recruitment and subsequent phosphorylation of the cytoplasmic transcription factors, STAT1 and STAT2, which translocate to the nucleus and associate with IRF9
to activate IFN genes.
miRNA Function Putative targets Reference miR-17-92 Down-regulated in IRF9
, RAB10,  imatinib treated TXNIP, TET2 CML cells miR-21 Antisense TXPAN2, LUM,  inhibition leads SUZ12, MSH2, to inhibition of PDZD2 migration and cell growth and induces apoptosis miR-203 Methylated in AML, RTKN2, AAK1,  CML, ALL, CLL.
The uterine LE/sGE in closest proximity to or adhered to conceptus trophectoderm express these unique genes because IFNT induces expression of IRF2 in uterine LE/sGE to silence expression of ESR1, STAT1, STAT2 and IRF9
. Therefore, this unique set of genes is induced by P4 and IFNT in uterine LE/sGE that lack both STAT1 and IRF9
This process promotes generation of the ISGF3 transcription factor, a complex of STAT1, STAT2, and IRF9
that accumulates in the nucleus.
These genes include Ets-1 and FoxP3 ; ITGAM and FcyRIIIA ; PD-1.3A, C4AQ0, and MBL ; AlFadhli (IRF9
, ABCA1, APOBEC3, CEACAM3, OSCAR, TNFA1P6, MMP9, and SLC4A1) ; FCGR3A and FCGR3B ; Tlr7 ; TBX21 and IFNG ; CD95 and CCR7 ; Fkbp11 ; JHDM1D and HDAC1-3 ; IL-28RA ; andpSTAT1 and ETS1 .
STAT1[alpha] and STAT2 form a trimeric complex with IFN regulatory factor 9 (IRF9
), known as ISGF3, followed by nuclear translocation and association with promoters of genes specifically activated by the type I IFNs.
miR-302d targets IRF9
, regulates interferonstimulated genes (ISG) expression, and protects against autoimmunity in mice .
During nonlethal PyNN67 infection, IRF9
participates in the production of IFN-I to control parasite growth .