HAT3.1, a novel Arabidopsis homeodomain protein containing a conserved cysteine‐rich region

Abstract

Homeodomain proteins have been shown to play a major role in the development of various organisms. A novel Arabidopsis homeodomain protein has been isolated based on its capability to interact with a DNA motif derived from the light-induced cab-E promoter of Nicotiana plumbaginifolia. The homeodomain of this protein, designated HAT3.1, differs substantially from those in other plant homeobox proteins identified so far. Furthermore, HAT3.1 is unique among other Arabidopsis proteins in that it does not contain a leucine zipper motif following the homeodomain. HAT3.1 is further characterized by an N-terminal region that shares substantial sequence similarity with the maize homeodomain protein Zmhox1a. Within this conserved region, the presence of eight regularly spaced cysteine/histidine residues was observed reminiscent of other metal-binding domains. Based on the strong evolutionary conservation of this domain, it is proposed that this region represents a novel protein-motif which is denoted PHD-finger (plant homeodomain-finger). In vitro DNA binding studies demonstrated that HAT3.1 is capable of interacting with any DNA fragment larger than 100 bp. Interestingly, a deletion of the N-terminal PHD-finger domain completely abolished DNA binding, suggesting that this region may play an important functional role in protein-protein or protein-DNA interaction. HAT3.1 mRNA was primarily detected in root tissue, implying a regulatory function of this protein in root development.

The cloning, mapping and expression of a novel gene, BRL, related to the AF10 leukaemia gene

“…Fusion constructs of Drosophila TRX containing the LAP/PHD domain were used to demonstrate that this region could bind zinc more strongly than other cysteine rich regions within this protein (Mazo et al, 1990). The N terminus of the plant protein HAT3.1 contains a LAP/PHD motif and it can bind non-speci®cally in vitro to any fragment of DNA greater than 100 bp (Schindler et al, 1993). Regulatory proteins such as those in the trithorax and polycomb group have the capacity to modify chromatin structure and it has been suggested that the LAP/PHD domain may be instrumental in this interaction (Aasland et al, 1995).…”

Histone H3K4me3 Binding Is Required for the DNA Repair and Apoptotic Activities of ING1 Tumor Suppressor

“…3). Substantial chemical shift changes were observed in 1 H, 15 N HSQC spectra of the 15 N-labeled PHD finger when the H3K4me3 peptide was gradually added. The largest resonance perturbations were seen in the Y212, C213, V218, Y220, G221, M223, G225, C226, E234, K246, G249 and K250 residues, which comprise the binding sites for trimethylated Lys 4 and Arg 2 and/or are involved in complimentary surface interactions and restraining the peptide backbone (Fig.…”

MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3)

“…Some information is known about several functional domains of MLL that suggest potential mechanisms of action. In the t(11;16), the resultant fusion product expressed from the der(11) chromosome contains the AT-hooks, the methyltransferase homology domain, and the repression domain of MLL and the carboxyl portion of CBP, whereas there is loss of the cysteine-rich C4HC3 PHD domains (20) and the activation domain of MLL in the der(11) product (18). What is also likely to be critical in generating the leukemia phenotype are the novel domains of CBP that are juxtaposed to MLL sequences.…”

“…Three AT-hook DNA-binding domains near the amino terminus also are found in the high-mobility group proteins HMG-I(Y) (15). MLL contains a region of homology to mammalian DNA methyltransferases, transcriptional activation and repression domains, and a cysteine-rich region that forms three C4HC3 zinc fingers [plant homeodomain (PHD) or leukemia-associated-protein domains] (16)(17)(18)(19)(20)(21). The PHD domain and the SET [Su(var)3-9 enhancer of zeste, and trithorax] domain at the carboxyl terminus are the regions most conserved with the Drosophila trithorax (trx) protein.…”