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Molecular and Cellular Biology, September 2009, p. 4640-4652, Vol. 29, No. 17
0270-7306/09/$08.00+0     doi:10.1128/MCB.00119-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Id1 Attenuates Notch Signaling and Impairs T-Cell Commitment by Elevating Deltex1 Expression{triangledown}

Hong-Cheng Wang, S. Scott Perry, and Xiao-Hong Sun*

Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, Oklahoma 73104

Received 26 January 2009/ Returned for modification 24 March 2009/ Accepted 29 May 2009

Complete inhibition of E protein transcription factors by Id1 blocks the developmental transition of CD4/CD8 double-negative 1 (DN1; CD44+ CD25–) thymocytes to the DN2 (CD44+ CD25+) stage. To understand the underlying mechanisms, we observed that mRNA levels of Deltex1, as well as Deltex4, were dramatically elevated in Id1-expressing thymocytes, which could result in developmental arrest by attenuating Notch function. In support of this hypothesis, we found that Deltex1 ablation enabled Id1-expressing progenitors to differentiate to the DN3 (CD44– CD25+) stage, which was accompanied by enhanced Notch1 expression in T-cell progenitors. Consistently, constitutive activation of Notch1 drove the differentiation of Id1-expressing progenitors to the DN3 stage. Furthermore, we showed that Gfi1b levels decreased, whereas GATA3 levels increased in Id1 transgenic thymocytes. When overexpressed, GATA3 was able to upregulate Deltex1 transcription. Thus, T-cell commitment may be controlled by the interplay among E proteins, Gfi1b, and GATA3 transcription regulators, which influence Notch function through the expression of Deltex1.

* Corresponding author. Mailing address: Program in Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104. Phone: (405) 271-7103. Fax: (405) 271-7128. E-mail: sunx{at}omrf.ouhsc.edu

{triangledown} Published ahead of print on 29 June 2009.

Molecular and Cellular Biology, September 2009, p. 4640-4652, Vol. 29, No. 17
0270-7306/09/$08.00+0     doi:10.1128/MCB.00119-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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