Secondary literature sources for the JmjN domain

For each of the hand selected primary papers associated with the JmjN domain, 100 neighbouring papers are retrieved from PubMed. If one of these neighbouring papers is referenced by more than two primary papers, it is shown in the table below.

Structural studies on a protein-binding zinc-finger domain of Eos revealboth similarities and differences to classical zinc fingers.

Westman BJ, Perdomo J, Matthews JM, Crossley M, Mackay JP
Biochemistry. 2004; 43: 13318-27

The oligomerization domain that is present at the C terminus ofIkaros-family proteins and the protein Trps-1 is important for the properregulation of developmental processes such as hematopoiesis. Remarkably,this domain is predicted to contain two classical zinc fingers (ZnFs),domains normally associated with the recognition of nucleic acids. Thepreference for protein binding by these predicted ZnFs is notwell-understood. We have used a range of methods to gain insight into thestructure of this domain. Circular dichroism, UV-vis, and NMR experimentscarried out on the C-terminal domain of Eos (EosC) revealed that the twoputative ZnFs (C1 and C2) are separable, i.e., capable of foldingindependently in the presence of Zn(II). We next determined the structureof EosC2 using NMR spectroscopy, revealing that, although the overall foldof EosC2 is similar to other classical ZnFs, a number of differencesexist. For example, the conformation of the C terminus of EosC2 appears tobe flexible and may result in a major rearrangement of the zinc ligands.Finally, alanine-scanning mutagenesis was used to identify the residuesthat are involved in the homo- and hetero-oligomerization of Eos, andthese results are discussed in the context of the structure of EosC. Thesestudies provide the first structural insights into how EosC mediatesprotein-protein interactions and contributes to our understanding of whyit does not exhibit high-affinity DNA binding.

Patterns of evolutionary conservation in the nesprin genes highlightprobable functionally important protein domains and isoforms.

Simpson JG, Roberts RG
Biochem Soc Trans. 2008; 36: 1359-67

The nesprins [also known as SYNEs (synaptic nuclear envelope proteins)]are a family of type II transmembrane proteins implicated in the tetheringof membrane-bound organelles and in the genetic aetiology of cerebellarataxia and Emery-Dreifuss muscular dystrophy. They are characterized by acommon structure of an SR (spectrin repeat) rod domain and a C-terminaltransmembrane KLS (klarsicht)/KASH [klarsicht/ANC-1 (anchorage 1)/SYNEhomology] domain which interacts with SUN [Sad1p/UNC (uncoordinated)-84]proteins in the nuclear envelope; most nesprins also have N-terminalactin-binding CH (calponin homology) domains. The genes encoding the threevertebrate nesprins (five in bony fish) and the small transmembraneactin-binding protein calmin are related to each other by ancientduplications and rearrangements. In the present paper, we collate sequencedata for nesprins and calmins across the vertebrate clade and use these tostudy evolutionary constraints acting on their genes. We show that the roddomains of the larger nesprins are composed almost entirely of unbrokenSR-like structures (74 in nesprin-1 and 56 in nesprin-2) and that theserange from poorly conserved purely structural elements to highly conservedregions with a presumed protein-protein interaction function. The analysissuggests several interesting regions for future study. We also assess theevolutionary and EST (expressed sequence tag) expression support fornesprin isoforms, both known and novel; our findings suggest thatsubstantial reassessment is required.

Evolution of NIN-like proteins in Arabidopsis, rice, and Lotus japonicus.

Schauser L, Wieloch W, Stougaard J
J Mol Evol. 2005; 60: 229-37

Genetic studies in Lotus japonicus and pea have identified Nin as a core symbiotic gene required for establishing symbiosis between legumes and nitrogen fixing bacteria collectively called Rhizobium. Sequencing of additional Lotus cDNAs combined with analysis of genome sequences from Arabidopsis and rice reveals that Nin homologues in all three species constitute small gene families. In total, the Arabidopsis and rice genomes encode nine and three NIN-like proteins (NLPs), respectively. We present here a bioinformatics analysis and prediction of NLP evolution. On a genome scale we show that in Arabidopsis, this family has evolved through segmental duplication rather than through tandem amplification. Alignment of all predicted NLP protein sequences shows a composition with six conserved modules. In addition, Lotus and pea NLPs contain segments that might characterize NIN proteins of legumes and be of importance for their function in symbiosis. The most conserved region in NLPs, the RWP-RK domain, has secondary structure predictions consistent with DNA binding properties. This motif is shared by several other small proteins in both Arabidopsis and rice. In rice, the RWP-RK domain sequences have diversified significantly more than in Arabidopsis. Database searches reveal that, apart from its presence in Arabidopsis and rice, the motif is also found in the algae Chlamydomonas and in the slime mold Dictyostelium discoideum. Thus, the origin of this putative DNA binding region seems to predate the fungus-plant divide.

Proteins with two SUMO-like domains in chromatin-associated complexes: theRENi (Rad60-Esc2-NIP45) family.

Novatchkova M, Bachmair A, Eisenhaber B, Eisenhaber F
BMC Bioinformatics. 2005; 6: 22-22

BACKGROUND: Post-translational modification by Small Ubiquitin-likeModifiers (SUMO) has been implicated in protein targeting, in themaintenance of genomic integrity and in transcriptional control. But thespecific molecular effects of SUMO modification on many target proteinsremain to be elucidated. Recent findings point at the importance ofSUMO-mediated histone NAD-dependent deacetylase (HDAC) recruitment intranscriptional regulation. RESULTS: We describe the RENi family ofSUMO-like domain proteins (SDP) with the unique feature of typicallycontaining two carboxy-terminal SUMO-like domains. Using sequence analyticevidence, we collect family members from animals, fungi and plants, mostprominent being yeast Rad60, Esc2 and mouse NIP45http://mendel.imp.univie.ac.at/SEQUENCES/reni/. Different proteins of thenovel family are known to interact directly with histone NAD-dependentdeacetylases (HDACs), structural maintenance of chromosomes (SMC)proteins, and transcription factors. In particular, the highly non-trivialdesignation of the first of the two successive SUMO-domains in non-plantRENi provides a rationale for previously published functionally impairedmutant variants. CONCLUSIONS: Till now, SUMO-like proteins have beenstudied exclusively in the context of their covalent conjugation to targetproteins. Here, we present the exciting possibility that SUMO domainproteins, similarly to ubiquitin modifiers, have also evolved in a secondline - namely as multi-domain proteins that are non-covalently attached totheir target proteins. We suggest that the SUMO stable fusion proteins ofthe RENi family, which we introduce in this work, might mimic SUMO andshare its interaction motifs (in analogy to the way that ubiquitin-likedomains mimic ubiquitin). This presumption is supported by parallels inthe spectrum of modified or bound proteins e.g. transcription factors andchromatin-associated proteins and in the recruitment of HDAC-activity.

SWIM, a novel Zn-chelating domain present in bacteria, archaea andeukaryotes.

Makarova KS, Aravind L, Koonin EV
Trends Biochem Sci. 2002; 27: 384-6

A previously undetected domain with a CxCx(n)CxH pattern of predictedzinc-chelating residues was identified in a variety of prokaryotic andeukaryotic proteins. These include bacterial ATPases of the SWI2/SNF2family, plant MuDR transposases and transposase-derived Far1 nuclearproteins, and vertebrate MEK kinase-1. This domain was designated SWIMafter SWI2/SNF2 and MuDR, and is predicted to have DNA-binding andprotein-protein interaction functions in different contexts.

Nickel ions increase histone H3 lysine 9 dimethylation and inducetransgene silencing.

Chen H, Ke Q, Kluz T, Yan Y, Costa M
Mol Cell Biol. 2006; 26: 3728-37

We have previously reported that carcinogenic nickel compounds decreasedglobal histone H4 acetylation and silenced the gpt transgene in G12Chinese hamster cells. However, the nature of this silencing is still notclear. Here, we report that nickel ion exposure increases global H3K9mono- and dimethylation, both of which are critical marks for DNAmethylation and long-term gene silencing. In contrast to the up-regulationof global H3K9 dimethylation, nickel ions decreased the expression andactivity of histone H3K9 specific methyltransferase G9a. Furtherinvestigation demonstrated that nickel ions interfered with the removal ofhistone methylation in vivo and directly decreased the activity of aFe(II)-2-oxoglutarate-dependent histone H3K9 demethylase in nuclearextract in vitro. These results are the first to show a histone H3K9demethylase activity dependent on both iron and 2-oxoglutarate. Exposureto nickel ions also increased H3K9 dimethylation at the gpt locus in G12cells and repressed the expression of the gpt transgene. An extendednickel ion exposure led to increased frequency of the gpt transgenesilencing, which was readily reversed by treatment with DNA-demethylatingagent 5-aza-2'-deoxycytidine. Collectively, our data strongly indicatethat nickel ions induce transgene silencing by increasing histone H3K9dimethylation, and this effect is mediated by the inhibition of H3K9demethylation.

Discovery of the principal specific transcription factors of Apicomplexaand their implication for the evolution of the AP2-integrase DNA bindingdomains.

Balaji S, Babu MM, Iyer LM, Aravind L
Nucleic Acids Res. 2005; 33: 3994-4006

The comparative genomics of apicomplexans, such as the malarial parasitePlasmodium, the cattle parasite Theileria and the emerging human parasiteCryptosporidium, have suggested an unexpected paucity of specifictranscription factors (TFs) with DNA binding domains that are closelyrelated to those found in the major families of TFs from other eukaryotes.This apparent lack of specific TFs is paradoxical, given that theapicomplexans show a complex developmental cycle in one or more hosts anda reproducible pattern of differential gene expression in course of thiscycle. Using sensitive sequence profile searches, we show that theapicomplexans possess a lineage-specific expansion of a novel family ofproteins with a version of the AP2 (Apetala2)-integrase DNA bindingdomain, which is present in numerous plant TFs. About 20-27 members ofthis apicomplexan AP2 (ApiAP2) family are encoded in differentapicomplexan genomes, with each protein containing one to four copies ofthe AP2 DNA binding domain. Using gene expression data from Plasmodiumfalciparum, we show that guilds of ApiAP2 genes are expressed in differentstages of intraerythrocytic development. By analogy to the plant AP2proteins and based on the expression patterns, we predict that the ApiAP2proteins are likely to function as previously unknown specific TFs in theapicomplexans and regulate the progression of their developmental cycle.In addition to the ApiAP2 family, we also identified two other novelfamilies of AP2 DNA binding domains in bacteria and transposons. Usingstructure similarity searches, we also identified divergent versions ofthe AP2-integrase DNA binding domain fold in the DNA binding region of thePI-SceI homing endonuclease and the C-terminal domain of the pleckstrinhomology (PH) domain-like modules of eukaryotes. Integrating thesefindings, we present a reconstruction of the evolutionary scenario of theAP2-integrase DNA binding domain fold, which suggests that it underwentmultiple independent combinations with different types of mobileendonucleases or recombinases. It appears that the eukaryotic versionshave emerged from versions of the domain associated with mobile elements,followed by independent lineage-specific expansions, which accompaniedtheir recruitment to transcription regulation functions.