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

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Perturbation of the expression level of IKAROS, a transcription factor critical during hematopoiesis, is associated with malignant transformation in mice and humans. The importance of IKAROS expression levels for the control of target-gene regulation was addressed in hematopoietic progenitor cells. The collaboration between IKAROS and the Nucleosome Remodeling and Deacetylase (NuRD) complex can promote gene activation or repression. IKAROS can also interact with the Positive-Transcription Elongation Factor b (P-TEFb) and the Protein Phosphatase 1 (PP1), an important P-TEFb regulator. Immunoaffinity purification of IKAROS interacting proteins and Fast Protein Liquid Chromatography analysis revealed a dynamic interaction between IKAROS, PP1 and the newly defined NuRD-P-TEFb complex. This complex can be targeted to specific genes in cells expressing high levels of IKAROS to promote productive transcription elongation. Based on our results we suggest that, in addition to P-TEFb, the NuRD complex and PP1 are required to facilitate transcription elongation of IKAROS-target genes and normal differentiation of hematopoietic progenitor cells.

Vyšlo v časopise: The IKAROS Interaction with a Complex Including Chromatin Remodeling and Transcription Elongation Activities Is Required for Hematopoiesis. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004827
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004827

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