NuRD and pluripotency: a complex balancing act.

Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Cell stem cell (Impact Factor: 23.56). 05/2012; 10(5):497-503. DOI: 10.1016/j.stem.2012.04.011
Source: PubMed

ABSTRACT Embryonic stem cells (ESCs) are defined by two essential features--pluripotency and self-renewal--whose balance requires the concerted action of signal transduction pathways, transcription factor networks, and epigenetic regulators. Recent findings have implicated the NuRD chromatin remodeling complex in the sophisticated choreography of ESC regulatory pathways.

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    Frontiers in Cell and Developmental Biology 01/2013; 1:4.
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    ABSTRACT: IKAROS is a critical regulator of hematopoietic cell fate and its dynamic expression pattern is required for proper hematopoiesis. In collaboration with the Nucleosome Remodeling and Deacetylase (NuRD) complex, it promotes gene repression and activation. It remains to be clarified how IKAROS can support transcription activation while being associated with the HDAC-containing complex NuRD. IKAROS also binds to the Positive-Transcription Elongation Factor b (P-TEFb) at gene promoters. Here, we demonstrate that NuRD and P-TEFb are assembled in a complex that can be recruited to specific genes by IKAROS. The expression level of IKAROS influences the recruitment of the NuRD-P-TEFb complex to gene regulatory regions and facilitates transcription elongation by transferring the Protein Phosphatase 1α (PP1α), an IKAROS-binding protein and P-TEFb activator, to CDK9. We show that an IKAROS mutant that is unable to bind PP1α cannot sustain gene expression and impedes normal differentiation of IkNULL hematopoietic progenitors. Finally, the knock-down of the NuRD subunit Mi2 reveals that the occupancy of the NuRD complex at transcribed regions of genes favors the relief of POL II promoter-proximal pausing and thereby, promotes transcription elongation.
    PLoS Genetics 12/2014; 10(12):e1004827. · 8.17 Impact Factor
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    ABSTRACT: Histones are chromatin proteins that are highly modified with many different types of post-translational modifications. These modifications act in concert to regulate a number of chromatin-related processes. However, identification and quantification of co-occurring histone post-translational modifications is challenging because there are many potential combinations of modifications and because the commonly used strategy of fragmenting proteins using trypsin or an alternative protease prior to LC-MS/MS analysis results in the loss of connectivity between modifications on different peptides. In this unit, mass spectrometric methods to analyze combinatorial histone modifications on histone tails (middle-down mass spectrometry) and on intact histones (top-down mass spectrometry) are described. Curr. Protoc. Protein Sci. 77:23.7.1-23.7.28. © 2014 by John Wiley & Sons, Inc.
    Current protocols in protein science / editorial board, John E. Coligan ... [et al.] 01/2014; 77:23.7.1-23.7.28.

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