title: GATA1 Binding Kinetics on Conformation-Specific Binding Sites Elicit Differential Transcriptional Regulation.
abstract: GATA1 organizes erythroid and megakaryocytic differentiation by orchestrating the expression of multiple genes that show diversified expression profiles. Here, we demonstrate that GATA1 monovalently binds to a single GATA motif (Single-GATA) while a monomeric GATA1 and a homodimeric GATA1 bivalently bind to two GATA motifs in palindromic (Pal-GATA) and direct-repeat (Tandem-GATA) arrangements, respectively, and form higher stoichiometric complexes on respective elements. The amino-terminal zinc (N) finger of GATA1 critically contributes to high occupancy of GATA1 on Pal-GATA. GATA1 lacking the N finger-DNA association fails to trigger a rate of target gene expression comparable to that seen with the wild-type GATA1, especially when expressed at low level. This study revealed that Pal-GATA and Tandem-GATA generate transcriptional responses from GATA1 target genes distinct from the response of Single-GATA. Our results support the notion that the distinct alignments in binding motifs are part of a critical regulatory strategy that diversifies and modulates transcriptional regulation by GATA1.
authors.affiliation: Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan Tohoku Medical Mega-Bank Organization, Tohoku University, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaneko
authors.affiliation: Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Daishi
authors.initials: D
authors.lastname: Ishihara
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan Tohoku Medical Mega-Bank Organization, Tohoku University, Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, Maryland, USA ceceliat@mail.nih.gov rshimizu@med.tohoku.ac.jp.
authors.forename: Cecelia D
authors.initials: CD
authors.lastname: Trainor
authors.affiliation: Department of Molecular Hematology, Tohoku University Graduate School of Medicine, Sendai, Japan Tohoku Medical Mega-Bank Organization, Tohoku University, Sendai, Japan ceceliat@mail.nih.gov rshimizu@med.tohoku.ac.jp.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D002478:Cells, Cultured; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism; D050982:GATA1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D011485:Protein Binding; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494689:Gata1 protein, mouse; D014157:Transcription Factors