Ikaros interacts with P-TEFb and cooperates with GATA–1 to enhance transcription elongation. Nucleic acids research

Ikaros is associated with both gene transcriptional activation and repression in lymphocytes. Ikaros acts also as repressor of human c-globin (huc-) 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 demon-strate that Ikaros is a developmental-specific activator of huc-gene expression in yolk sac eryth-roid cells. Molecular analysis in primary cells revealed that Ikaros interacts with Gata-1 and favors Brg1 recruitment to the human b-globin Locus Control Region and the huc-promoters, supporting long-range chromatin interactions between these regions. Additionally, we demon-strate that Ikaros contributes to transcription initi-ation and elongation of the huc-genes, since it is not only required for TBP and RNA Polymerase II (Pol II) assembly at the huc-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 huc-promoters. Our results show that Ikaros exerts dual functionality during gene activation, by promoting efficient transcription initiation and elongation