Ikaros directly represses the notch target gene Hes1 in a leukemia T cell line: implications for CD4 regulation.
Ikaros and Notch1, two regulators of gene transcription, are critically important at many stages of T cell development. Deregulation of Ikaros and Notch activities cooperate to promote T cell leukemogenesis, providing evidence that they function in converging pathways in developing T cells. In this report, a mechanism for Ikaros:Notch cooperativity is described, revealing a non-redundant role for Ikaros in regulating expression of the Notch target gene Hes1 in a leukemia T cell line. We provide evidence that Ikaros directly represses Hes1 in concert with the transcriptional repressor, RBP-Jkappa, allowing for cross-talk between Notch and Ikaros that impacts regulation of CD4 expression. Taken together, these data describe a potential mechanism for Ikaros' function during T cell development and define Ikaros as an obligate repressor of Hes1.
Kathrein
Katie L
KL
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Chari
Sheila
S
Winandy
Susan
S
D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015704:CD4 Antigens / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000378:metabolism*; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D051881:Receptor, Notch1 / Q000378:metabolism*; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D015704:CD4 Antigens; D018398:Homeodomain Proteins; D051740:Ikaros Transcription Factor; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C497762:Notch1 protein, mouse; C497238:Zfpn1a1 protein, mouse