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Review
. 2012 Apr;24(2):146-52.
doi: 10.1016/j.coi.2012.01.015. Epub 2012 Feb 16.

The role of STAT5 in lymphocyte development and transformation

Lynn M Heltemes-Harris  1 , Michael A Farrar
Affiliations
Review

The role of STAT5 in lymphocyte development and transformation

Lynn M Heltemes-Harris et al. Curr Opin Immunol. 2012 Apr.

Abstract

STAT5 plays a crucial role in B and T lymphocyte development. However, whether STAT5 primarily plays a role as a permissive factor, involved in lymphocyte survival, or an instructive factor, involved in lymphocyte differentiation, has been unclear. In addition, while STAT5 has been suggested to act as a transcriptional repressor, the mechanism by which it represses transcription was undefined. Recent reports have begun to shed new light on these roles for STAT5 in lymphocyte development, transcriptional repression, and leukemic transformation.

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Figures

Figure 1
Figure 1
Overview of lymphocyte development with an emphasis on the role of STAT5. The green arrows mark the different stages of development where STAT5 plays a positive role in development of different lymphocyte subsets. The red arrow marks where STAT5-dependent inhibition is required for normal development.
Figure 2
Figure 2
Model for how STAT5 might regulate gene transcription in T and B cell development. In some instances, transient expression of STAT5 correlates with an instructive role in development. As illustrated for Ebf1 and Foxp3, STAT5 activation may initiate transcription but continued expression of genes is maintained by positive feedback loops that are STAT5-independent. Therefore, these genes would only require an initial threshold level of STAT5 signaling without a need for continuous STAT5 signaling. In contrast, continuous STAT5 signaling is required for permissive genes such as Mcl1, Bcl2, and Cyclin D2, although it can be required for instructive factors, such as Runx3, as well.
Figure 3
Figure 3
STAT5 repressive mechanism at the light chain immunoglobulin locus. STAT5 homodimers translocate to the nucleus following cytokine activation. In the nucleus, STAT5 may bind as a tetramer to tandemly repeated STAT5 DNA-binding sites. These tetrameric complexes are capable of recruiting EZH2 and other members of the polycomb repressor family. The resulting complex generates repressive chromatin via H3K27 trimethylation (H3K27me3).
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