TY - JOUR
T1 - GATA1 binding kinetics on conformation-specific binding sites elicit differential transcriptional regulation
AU - Hasegawa, Atsushi
AU - Kaneko, Hiroshi
AU - Ishihara, Daishi
AU - Nakamura, Masahiro
AU - Watanabe, Akira
AU - Yamamoto, Masayuki
AU - Trainor, Cecelia D.
AU - Shimizu, Ritsuko
N1 - Funding Information:
This work, including the efforts of Masayuki Yamamoto, was funded by Ministry of Education, Culture, Sports, Science, and Technology (MEXT) (22118002). This work, including the efforts of Cecelia Trainor, was funded by HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This work, including the efforts of Ritsuko Shimizu, was funded by Japan Society for the Promotion of Science (JSPS) (24659142 and 15H04759). This work, including the efforts of Atsushi Hasegawa, was funded by Japan Society for the Promotion of Science (JSPS). This work, including the efforts of Masayuki Yamamoto, was funded by Naito Foundation. This work, including the efforts of Masayuki Yamamoto, was funded by Japan Agency for Medical Research and Development (AMED). This work, including the efforts of Ritsuko Shimizu, was funded by Japan Agency for Medical Research and Development (AMED). This work, including the efforts of Masayuki Yamamoto, was funded by Takeda Medical Research Foundation.
Publisher Copyright:
© 2016, American Society for Microbiology. All Rights Reserved.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.00017-16
DO - 10.1128/MCB.00017-16
M3 - Article
C2 - 27215385
AN - SCOPUS:84982823030
SN - 0270-7306
VL - 36
SP - 2151
EP - 2167
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 15
ER -