| First Author | Stratigi K | Year | 2015 |
| Journal | Proc Natl Acad Sci U S A | Volume | 112 |
| Issue | 13 | Pages | E1577-86 |
| PubMed ID | 25770217 | Mgi Jnum | J:220683 |
| Mgi Id | MGI:5635938 | Doi | 10.1073/pnas.1502182112 |
| Citation | Stratigi K, et al. (2015) Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch in allelic gene expression. Proc Natl Acad Sci U S A 112(13):E1577-86 |
| abstractText | Physiological processes rely on the regulation of total mRNA levels in a cell. In diploid organisms, the transcriptional activation of one or both alleles of a gene may involve trans-allelic interactions that provide a tight spatial and temporal level of gene expression regulation. The mechanisms underlying such interactions still remain poorly understood. Here, we demonstrate that lipopolysaccharide stimulation of murine macrophages rapidly resulted in the actin-mediated and transient homologous spatial proximity of Tnfalpha alleles, which was necessary for the mono- to biallelic switch in gene expression. We identified two new complementary long noncoding RNAs transcribed from the TNFalpha locus and showed that their knockdown had opposite effects in Tnfalpha spatial proximity and allelic expression. Moreover, the observed spatial proximity of Tnfalpha alleles depended on pyruvate kinase muscle isoform 2 (PKM2) and T-helper-inducing POZ-Kruppel-like factor (ThPOK). This study suggests a role for lncRNAs in the regulation of somatic homologous spatial proximity and allelic expression control necessary for fine-tuning mammalian immune responses. |
