TY - JOUR
T1 - Loss of CARM1 results in hypomethylation of thymocyte cyclic AMP-regulated phosphoprotein and deregulated early T cell development
AU - Kim, Jeesun
AU - Lee, Jaeho
AU - Yadav, Neelu
AU - Wu, Qi
AU - Carter, Carla
AU - Richard, Stéphane
AU - Richie, Ellen
AU - Bedford, Mark T.
PY - 2004/6/11
Y1 - 2004/6/11
N2 - The coactivator-associated arginine methyltransferase, CARM1, is a positive regulator of transcription. Using high density protein arrays, we have previously identified in vitro substrates for CARM1. One of these substrates, TARPP (thymocyte cyclic AMP-regulated phosphoprotein), is expressed specifically in immature thymocytes. Here, we have demonstrated that TARPP is arginine-methylated at a single residue, Arg650, both in vitro and in vivo. In addition, recombinant TARPP is not methylated by extracts from Carm1-/- cells, indicating that there is no redundancy in this pathway. We show that thymi from Carm1-/- embryos (E18.5) have a 5-10-fold reduction in cellularity compared with wild type littermates. Flow cytometric analysis of thymocytes revealed a decrease in the relative proportion of double negative thymocytes in Carm1-/- embryos because of a partial developmental arrest in the earliest thymocyte progenitor subset. These results demonstrate that CARM1 plays a significant role in promoting the differentiation of early thymocyte progenitors, possibly through its direct action on TARPP.
AB - The coactivator-associated arginine methyltransferase, CARM1, is a positive regulator of transcription. Using high density protein arrays, we have previously identified in vitro substrates for CARM1. One of these substrates, TARPP (thymocyte cyclic AMP-regulated phosphoprotein), is expressed specifically in immature thymocytes. Here, we have demonstrated that TARPP is arginine-methylated at a single residue, Arg650, both in vitro and in vivo. In addition, recombinant TARPP is not methylated by extracts from Carm1-/- cells, indicating that there is no redundancy in this pathway. We show that thymi from Carm1-/- embryos (E18.5) have a 5-10-fold reduction in cellularity compared with wild type littermates. Flow cytometric analysis of thymocytes revealed a decrease in the relative proportion of double negative thymocytes in Carm1-/- embryos because of a partial developmental arrest in the earliest thymocyte progenitor subset. These results demonstrate that CARM1 plays a significant role in promoting the differentiation of early thymocyte progenitors, possibly through its direct action on TARPP.
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U2 - 10.1074/jbc.M402544200
DO - 10.1074/jbc.M402544200
M3 - Article
C2 - 15096520
AN - SCOPUS:2942537778
SN - 0021-9258
VL - 279
SP - 25339
EP - 25344
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 24
ER -