| First Author | Bottardi S | Year | 2011 |
| Journal | Nucleic Acids Res | Volume | 39 |
| Issue | 9 | Pages | 3505-19 |
| PubMed ID | 21245044 | Mgi Jnum | J:182882 |
| Mgi Id | MGI:5317044 | Doi | 10.1093/nar/gkq1271 |
| Citation | Bottardi S, et al. (2011) Ikaros interacts with P-TEFb and cooperates with GATA-1 to enhance transcription elongation. Nucleic Acids Res 39(9):3505-19 |
| abstractText | Ikaros is associated with both gene transcriptional activation and repression in lymphocytes. Ikaros acts also as repressor of human gamma-globin (hugamma-) gene transcription in fetal and adult erythroid cells. Whether and eventually, how Ikaros can function as a transcriptional activator in erythroid cells remains poorly understood. Results presented herein demonstrate that Ikaros is a developmental-specific activator of hugamma-gene expression in yolk sac erythroid cells. Molecular analysis in primary cells revealed that Ikaros interacts with Gata-1 and favors Brg1 recruitment to the human beta-globin Locus Control Region and the hugamma-promoters, supporting long-range chromatin interactions between these regions. Additionally, we demonstrate that Ikaros contributes to transcription initiation and elongation of the hugamma-genes, since it is not only required for TBP and RNA Polymerase II (Pol II) assembly at the hugamma-promoters but also for conversion of Pol II into the elongation-competent phosphorylated form. In agreement with the latter, we show that Ikaros interacts with Cyclin-dependent kinase 9 (Cdk9), which contributes to efficient transcription elongation by phosphorylating the C-terminal domain of the large subunit of Pol II on Serine 2, and favours Cdk9 recruitment to hugamma-promoters. Our results show that Ikaros exerts dual functionality during gene activation, by promoting efficient transcription initiation and elongation. |
