title: Cutting edge: IRF8 regulates Bax transcription in vivo in primary myeloid cells.
abstract: A prominent phenotype of IRF8 knockout (KO) mice is the uncontrolled expansion of immature myeloid cells. The molecular mechanism underlying this myeloproliferative syndrome is still elusive. In this study, we observed that Bax expression level is low in bone marrow preginitor cells and increases dramatically in primary myeloid cells in wt mice. In contrast, Bax expression level remained at a low level in primarymyeloid cells in IRF8 KO mice. However, in vitro IRF8 KO bone marrow-differentiated myeloid cells expressed Bax at a level as high as that in wild type myeloid cells. Furthermore, we demonstrated that IRF8 specifically binds to the Bax promoter region in primary myeloid cells. Functional analysis indicated that IRF8 deficiency results in increased resistance of the primary myeloid cells to Fas-mediated apoptosis. Our findings show that IRF8 directly regulates Bax transcription in vivo, but not in vitro during myeloid cell lineage differentiation.
authors.affiliation: Key Laboratory of Gene Engineering of Ministry of Education, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.
authors.forename: Jine
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Hu
authors.forename: Mary
authors.initials: M
authors.lastname: Zimmerman
authors.forename: Christina M
authors.initials: CM
authors.lastname: Torres
authors.forename: Dafeng
authors.initials: D
authors.lastname: Yang
authors.forename: Sylvia B
authors.initials: SB
authors.lastname: Smith
authors.forename: Kebin
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic / Q000276:immunology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D013163:Splenomegaly / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000276:immunology*; D051028:bcl-2-Associated X Protein / Q000235:genetics* / Q000378:metabolism*; D000099185:Interferon Regulatory Factor-8
chemical_list: D050835:Interferon Regulatory Factors; D051028:bcl-2-Associated X Protein; D000099185:Interferon Regulatory Factor-8; C494827:Bax protein, mouse