Modulator recognition factor-2 (MRF2) is a member of the AT-rich interaction domain (ARID) family of transcription factors (also known as ARID5B
or Desrt ).
As revealed by the RI parameter, TFs with the lowest values have a high out-degree, but at the same time, they present a high in-degree, such is the case of ZHX2, ADNP, SMAD6, POU3F1, GTF2A1, ZIC2, POU6F1, TFAP4, ARID5B, or RUNX1.
In- Out- transcript Gene degree degree RI count RUNX1 155 556 0.517749925 9382.91 ARID5B 114 392 0.49206167 12.885 TFAP4 190 632 0.483369442 642.65 POU6F1 87 268 0.442040072 229.68 ZIC2 135 407 0.438502347 10132.46 GTF2A1 100 253 0.357562642 1219.94 POU3F1 80 198 0.331108025 4.585 SMAD6 175 408 0.289214257 2936.75 ADNP 132 292 0.256880007 651.685 Table 3: The top 5 highest and lowest values of TFs in the RegulonDB E.
Normally, a protein called ARID5B squats on the enhancer and prevents it from dialing up activity of the fat-determining genes.
Caption: Fat Switch Energy-burning beige fat is made when a protein called ARID5B prevents a bit of DNA that acts as an enhancer from turning on two faraway genes (IRX3 and IRX5).
Twenty-one significantly mutated genes (candidate pathogenic driver genes) have been identified in the hypermutated/microsatellite-unstable subgroup (Table 1), including 11 genes (ARID5B, CSDE1, CTCF, GIGYF2, HIST1H2BD, LIMCH1, MIR1277, NKAP, RBMX, TNFAIP6, ZFHX3) that were not previously known to be significantly mutated in endometrial carcinoma.
That is not to say that chromatin-remodeling genes and genes of the ubiquitin ligase complex are not also perturbed in the endometrioid subtype; indeed, a number of chromatin-remodeling genes, such as ARID1A, ARID5B, CTCF, and CHD4, are also causal or candidate driver genes in molecular subgroups dominated by endometrioid endometrial tumors (Table 1).
Novel mutations also were discovered in the SWI/SNF chromatin remodeling complex gene ARID5B
. About 10% of endometrioid tumors had markedly increased transversion mutations and newly identified mutations in POLE, a gene involved in nuclear DNA replication and repair.
Jude Pharmaceutical Sciences chair and the paper's senior author, estimated that individuals who inherited variations in the genes, known as ARID5B and IKZF1, were almost twice as likely to develop ALL.
The inherited variations in ARID5B might also influence patient response to chemotherapy, particularly to the drug methotrexate.
"These findings may identify a new marker that could be used to help decide on doses of methotrexate in patients with varying ARID5B status."