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J Biol Chem August 14, 2015; 290 (33): 20273-83.

JmjC Domain-containing Protein 6 (Jmjd6) Derepresses the Transcriptional Repressor Transcription Factor 7-like 1 (Tcf7l1) and Is Required for Body Axis Patterning during Xenopus Embryogenesis.

Zhang X , Gao Y , Lu L , Zhang Z , Gan S , Xu L , Lei A , Cao Y .

Tcf7l1 (also known as Tcf3) is a bimodal transcription factor that plays essential roles in embryogenesis and (embryonic and adult) stem cells. On the one hand, Tcf7l1 works as transcriptional repressor, via the recruitment of Groucho-related transcriptional co-repressors, to repress the transcription of Wnt target genes, and on the other, it activates Wnt target genes when Wnt-activated β-catenin interacts with it. However, how its activity is modulated is not well understood. Here, we demonstrate that a JmjC-domain containing protein, Jmjd6, interacts with Tcf7l and derepresses Tcf7l. We show that Jmjd6 binds to a region of Tcf7l1 that is also responsible for Groucho interaction, thus making it possible that Jmjd6 binding displaces the Groucho transcriptional co-repressor from Tcf7l1. Moreover, we manifest that Jmjd6 antagonizes the repression effect of Tcf7l1 on target gene transcription and is able to enhance the β-catenin-induced gene activation, and vice versa, inhibition of Jmjd6 activity compromises the gene activation in both cells and Xenopus early embryos. We also show that jmjd6 is both maternally and zygotically transcribed during Xenopus embryogenesis. Loss of Jmjd6 function causes defects in anterio-posterior (A-P) body axis formation and downregulation of genes that are involved in A-P axis patterning. The results elucidate a novel mechanism underlying the regulation of Tcf7l1 activity and the regulation of embryonic body axis formation.

PubMed ID: 26157142
PMC ID: PMC4536435
Article link: J Biol Chem

Genes referenced: ag1 cer1 chrd.1 dkk1 foxa4 gsc jarid2 jmjd6 nodal1 nodal3.1 odc1 otx2 sia1 tbl1x tcf7l1 xpo1

Morpholinos referenced: jmjd6 MO1 tcf7l1 MO2

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Andoniadou, 2011, Pubmed, Xenbase [+]

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