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Molecular and Cellular Biology, March 2009, p. 1515-1525, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01239-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Requirement of Split ends for Epigenetic Regulation of Notch Signal-Dependent Genes during Infection-Induced Hemocyte Differentiation{triangledown} ,{dagger}

Li Hua Jin,1 Jung Kyoon Choi,1 Byungil Kim,1 Hwan Sung Cho,1 Jihyun Kim,2 Jeongsil Kim-Ha,2 and Young-Joon Kim1*

Department of Biochemistry, Yonsei University, Seoul 120-749, Republic of Korea,1 Department of Molecular Biology, Sejong University, Seoul 143-747, Republic of Korea2

Received 5 August 2008/ Returned for modification 17 October 2008/ Accepted 30 December 2008

Drosophila producing a mutant form of the putative transcription coregulator, Split ends (Spen), originally identified in the analysis of neuronal development, display diverse immune defects. In order to understand the role of Spen in the innate immune response, we analyzed the transcriptional defects associated with spen mutant hemocytes and their relationship to the Notch signaling pathways. Spen is regulated by the Notch pathway in the lymph glands and is required for Notch-dependent activation of a large number of genes involved in energy metabolism and differentiation. Analysis of the epigenetic marks associated with Spen-dependent genes indicates that Spen performs its function as a coactivator by regulating chromatin modification. Intriguingly, expression of the Spen-dependent genes was transiently downregulated in a Notch-dependent manner by the Dif activated upon recognition of pathogen-associated molecules, demonstrating the existence of cross talk between hematopoietic regulation and the innate immune response. Our observations reveal a novel connection between the Notch and Toll/IMD signaling pathways and demonstrate a coactivating role for Spen in activating Notch-dependent genes in differentiating cells.

* Corresponding author. Mailing address: Department of Biochemistry, Yonsei University, 134 Sinchon-dong, Seodaemoon-ku, Seoul 120-749, Republic of Korea. Phone: 82-2-2123-2628. Fax: 82-2-312-8834. E-mail: yjkim{at}yonsei.ac.kr

{triangledown} Published ahead of print on 12 January 2009.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, March 2009, p. 1515-1525, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01239-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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