Premium
CCAR 1/ C o C o A pair‐mediated recruitment of the Mediator defines a novel pathway for GATA 1 function
Author(s) -
Mizuta Shumpei,
Minami Tomoya,
Fujita Haruka,
Kaminaga Chihiro,
Matsui Keiji,
Ishino Ruri,
Fujita Azusa,
Oda Kasumi,
Kawai Asami,
Hasegawa Natsumi,
Urahama Norinaga,
Roeder Robert G.,
Ito Mitsuhiro
Publication year - 2014
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12104
Subject(s) - gata1 , transcription factor , biology , mediator , coactivator , transcription (linguistics) , microbiology and biotechnology , erythropoiesis , gene , genetics , medicine , linguistics , philosophy , anemia
The MED1 subunit of the Mediator transcriptional coregulator complex coactivates GATA1 and induces erythropoiesis. Here, we show the dual mechanism of GATA1‐ and MED1‐mediated transcription. MED1 expression levels in K562 erythroleukemia cells paralleled the levels of GATA1‐targeted gene transcription and erythroid differentiation. An N‐terminal fragment of MED1, MED1(1–602), which is incapable of interacting with GATA1, enhanced GATA1‐targeted gene transcription and erythroid differentiation, and introduction of MED1(1–602) into Med1 −/− mouse embryonic fibroblasts (MEFs) partially rescued GATA1‐mediated transcription. The C‐terminal zinc‐finger domain of GATA1 interacts with the MED1(1–602)‐interacting coactivator CCAR1, CoCoA and MED1(681–715). CCAR1 and CoCoA synergistically enhanced GATA1‐mediated transcription from the γ‐globin promoter in MEFs. Recombinant GATA1, CCAR1, CoCoA and MED1(1–602) formed a complex in vitro , and GATA1, CCAR1, CoCoA and MED1 were recruited to the γ‐globin promoter in K562 cells during erythroid differentiation. Therefore, in addition to the direct interaction between GATA1 and MED1, CoCoA and CCAR1 appear to relay the GATA1 signal to MED1, and multiple modes of the GATA1‐MED1 axis may help to fine‐tune GATA1 function during GATA1‐mediated homeostasis events.