Epigenetic Regulation of Lymphocyte Development by Sven Heinz, Christopher K. Glass (auth.), Cornelis Murre

By Sven Heinz, Christopher K. Glass (auth.), Cornelis Murre (eds.)

The stories defined during this quantity function a place to begin to familiarize one self with the multifarious variations in epigenetic designs that orchestrate the development of constructing blood cells. additionally they may perhaps function a normal paradigm for the mechanisms that underpin the regulate of eukaryotic gene expression.

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Bone marrow B cell development exhibited a striking compound phenotype in Ebf1+/-Runx1+/-, or ERhet mice (Lukin et al. 2010). Most effects were apparent at the pro-B-pre-B boundary and at subsequent stages. This disruption occurs later than effects observed in Ebf1+/-Tcfe2a+/- mice. Reduced levels of EBF1 alone decreased the frequency of Igk light chain gene rearrangements significantly. Other effects of the compound genotype included: (1) delayed shut off of early progenitor-specific genes (c-Kit, Vpreb1 and Igll1), (2) delayed activation of stage-specific markers (Ikzf3, Cd25 and Cd2) and (3) loss of most pre-B, immature and mature B cells, which normally express the highest levels of EBF1.

2010). 1 (Sfpi1), Gfi1 (Gfi1), Ikaros (Ikzf1) and E2A (multiple proteins expressed by the Tcfe2a gene) (Reviewed in Ramirez et al. 2010), which regulate cells’ decisions to attain myeloid versus lymphoid fates. The concentration, or dosage, of regulatory factors helps determine the priming of cell differentiation (lineage priming) and subsequent fate decisions. 1, respectively (Dekoter and Singh 2000). 1 (Spooner et al. 2009). Ikaros directs hematopoietic progenitors by promoting B cell-specific gene expression and Ig heavy chain gene rearrangements (Reynaud et al.

Hagman et al. recognition of bases within both half-sites by each EBF1 monomer. Residues within an extended loop between the b-strands of the DBD’s amino-terminus and a carboxyl-terminal loop recognize the invariant bases within the major groove of one half-site. The zinc knuckle makes contacts with the minor groove of the other half-site. Thus, contacts made by each monomer within the homodimer assemble a symmetric clamp that extends across both half-sites of the palindrome. This configuration explains the requirement for a two base pair spacer between the two half-sites recognized by EBF1 (Travis et al.

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