title: An Ikaros Promoter Element with Dual Epigenetic and Transcriptional Activities.
abstract: Ikaros DNA binding factor plays critical roles in lymphocyte development. Changes in Ikaros expression levels during lymphopoiesis are controlled by redundant but also unique regulatory elements of its locus that are critical for this developmental process. We have recently shown that Ikaros binds its own locus in thymocytes in vivo. Here, we evaluated the role of an Ikaros binding site within its major lympho-myeloid promoter. We identified an Ikaros/Ets binding site within a promoter sub-region that was highly conserved in mouse and human. Deletion of this binding site increased the percentage of the reporter-expressing mouse lines, indicating that its loss provided a more permissive chromatin environment. However, once transcription was established, the lack of this site decreased transcriptional activity. These findings implicate a dual role for Ikaros/Ets1 binding on Ikzf1 expression that is exerted at least through its promoter.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States of America.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Perotti
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States of America.
authors.forename: Katia
authors.initials: K
authors.lastname: Georgopoulos
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, United States of America.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Yoshida
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D060168:Thymocytes / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C497239:IKZF1 protein, human; C497238:Zfpn1a1 protein, mouse; D049452:Green Fluorescent Proteins; D051740:Ikaros Transcription Factor