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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Int+J+Hematol
2014 ; 100
(3
): 220-9
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Ikaros fingers on lymphocyte differentiation
#MMPMID25085254
Yoshida T
; Georgopoulos K
Int J Hematol
2014[Sep]; 100
(3
): 220-9
PMID25085254
show ga
The Ikaros family of DNA-binding proteins are critical regulators of lymphocyte
differentiation. In multipotent, hematopoietic progenitors, Ikaros supports
transcriptional priming of genes promoting lymphocyte differentiation. Ikaros
targets the Nucleosome Remodeling Deacetylase (NuRD) complex to lymphoid lineage
genes, thereby increasing chromatin accessibility and transcriptional priming.
After lymphoid lineage specification, Ikaros expression is raised to levels
characteristic of intermediate B cell and T cell precursors, which is necessary
to support maturation and prevent leukemogenesis. Loss of Ikaros in T cell
precursors allows the NuRD complex to repress lymphocyte genes and extends its
targeting to genes that support growth and proliferation, causing their
activation and triggering a cascade of events that leads to leukemogenesis. Loss
of Ikaros in B cell precursors blocks differentiation and perpetuates stromal
adhesion by enhancing integrin signaling. The combination of integrin and
cytokine signaling in Ikaros-deficient pre-B cells promotes their survival and
self-renewal. The stages of lymphocyte differentiation that are highly dependent
on Ikaros are underscored by changes in Ikaros transcription, supported by a
complex network of stage-specific regulatory networks that converge upon the
Ikzf1 locus. It is increasingly apparent that understanding the regulatory
networks that operate upstream and downstream of Ikaros is critical not only for
our understanding of normal lymphopoiesis, but also in placing the right finger
on the mechanisms that support hematopoietic malignancies in mouse and human.
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