The IKAROS Interaction with a Complex Including Chromatin Remodeling and Transcription Elongation Activities Is Required for Hematopoiesis

• DOI: 10.1371/journal.pgen.1004827
• Publication Date: 2014-12-04T19:33:05Z
• Authors: Stefania Bottardi; Lionel Mavoungou; Helen Pak; Salima Daou; Vincent Bourgoin; Yahia A. Lakehal; El Bachir Affar; Eric Milot
• Keywords: P-TEFb; RNA polymerase II; Transcription

IKAROS is a critical regulator of hematopoietic cell fate and its dynamic expression pattern required for proper hematopoiesis. In collaboration with the Nucleosome Remodeling Deacetylase (NuRD) complex, it promotes gene repression activation. It remains to be clarified how can support transcription activation while being associated HDAC-containing complex NuRD. also binds Positive-Transcription Elongation Factor b (P-TEFb) at promoters. Here, we demonstrate that NuRD P-TEFb are assembled in recruited specific genes by IKAROS. The level influences recruitment NuRD-P-TEFb regulatory regions facilitates elongation transferring Protein Phosphatase 1α (PP1α), an IKAROS-binding protein activator, CDK9. We show mutant unable bind PP1α cannot sustain impedes normal differentiation IkNULL progenitors. Finally, knock-down subunit Mi2 reveals occupancy transcribed favors relief POL II promoter-proximal pausing thereby, elongation.