Requirement of Split ends for epigenetic regulation of Notch signal-dependent genes during infection-induced hemocyte differentiation.
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.
Jin
Li Hua
LH
Department of Biochemistry, Yonsei University, Seoul, Republic of Korea.
Choi
Jung Kyoon
JK
Kim
Byungil
B
Cho
Hwan Sung
HS
Kim
Jihyun
J
Kim-Ha
Jeongsil
J
Kim
Young-Joon
YJ
D000818:Animals; D052982:Beauveria / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000276:immunology / Q000382:microbiology / Q000502:physiology*; D044127:Epigenesis, Genetic; D006434:Hemocytes / Q000166:cytology* / Q000382:microbiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C497759:N protein, Drosophila; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D051880:Receptors, Notch; C402387:Spen protein, Drosophila