Solution structure of the AT‐rich interaction domain of Jumonji/JARID2

Abstract

Jumonji/JARID2 (Jmj) is a transcriptional repressor protein, which plays important roles in development, cell growth and gene expression.1–3 For example, recent studies have revealed that Jmj represses the expression of cyclin D1, a key component of the cell cycle machinery, by inducing histone H3 lysine 9 (H3-K9) methylation in the complex with G9a and GLP, which are H3-K9 methyltransferase proteins.4,5 In addition, Jmj has been shown to repress atrial natriuretic factor (ANF) gene expression, by interacting with the transcriptional activities of the cardiac transcription factors, Nkx2.5 and GATA4.6 Therefore, it is believed that Jmj may use different regulatory mechanisms with multiple target genes. The Jmj protein consists of at least six structural and functional domains [Fig. 1(A)]: the nuclear localization signal (NLS) domain, the transcriptional repressor domain, the JmjN domain, the AT-rich interaction domain (ARID), the JmjC domain and the Zinc finger-like C5HC2 domain.3 The ARID domain7,8 is a distinct DNA-binding module and binds to DNA through a long loop that connects the helices of a helix-turn-helix (HTH) motif, and therefore this HTH motif is called as a noncanonical HTH motif.9,10 ARID domains have both functional and structural diversities.7,8 For example, the Dri-ARID9,10 and Mrf2-ARID11 domains interact with their specific AT-rich DNA sequences, while the RBP2-ARID domain binds to a GC-rich CCGCC DNA sequence.12 Furthermore, the SWI1-ARID domain reportedly interacts with nonspecific DNA sequences.13 So far, three structural classes have been represented: (i) the minimal ARID domain (six a-helices), (ii) both the Nand C-terminal extended ARID domain and (iii) the N-terminal extended ARID domain. However, the structure of the Cterminal extended ARID domain has not been determined yet. We previously performed NMR analyses of the Jmj-ARID domain consisting of residues Leu615Lys730.14 The secondary structure prediction from the NMR data revealed that the Jmj-ARID domain may possess an additional helix at the C-terminus. Thus, the JmjARID domain seems to be a good candidate to represent the C-terminal ARID domain. Here we report the first NMR-derived structure of the ARID of Jumonji/JARID2.