The PHD domain of the sea urchin RAG2 homolog, SpRAG2L, recognizes dimethylated lysine 4 in histone H3 tails

Wilson, David R.; Norton, Darrell D.; Fugmann, Sebastian D.

doi:10.1016/j.dci.2008.03.012

Cited by 19 publications

(17 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here we show that both Drosophila and human PHF7 can directly associate with dimethylated H3K4, indicating that PHF7 is indeed a histone code reader. It is uncommon for PHD domains to associate preferentially with H3K4me2 over H3K4me3, but this specificity has been observed previously (Kim and Buratowski, 2009; Wilson et al, 2008), and is likely important for how PHF7 modulates expression of its targets. Both di- and trimethylated H3K4 are found at actively transcribed genes, but H3K4me2 is normally localized at the 5' end of coding sequences, downstream of H3K4me3 which is near promoters (Barrera and Ren, 2006).…”

Section: Discussionmentioning

confidence: 64%

Phf7 Controls Male Sex Determination in the Drosophila Germline

2012

View full text Add to dashboard Cite

Summary Establishment of germline sexual identity is critical for production of male and female germline stem cells, and sperm vs. eggs. Here we identify PHD Finger Protein 7 (PHF7) as an important factor for male germline sexual identity in Drosophila. PHF7 exhibits male-specific expression in early germ cells, germline stem cells and spermatogonia. It is required for germline stem cell maintenance and gametogenesis in males, whereas ectopic expression in female germ cells ablates the germline. Strikingly, expression of PHF7 promotes spermatogenesis in XX germ cells when they are present in a male soma. PHF7 homologs are also specifically expressed in the mammalian testis, and human PHF7 rescues Drosophila Phf7 mutants. PHF7 associates with chromatin and both the human and fly proteins bind histone H3 N-terminal tails with a preference for dimethyl lysine 4 (H3K4me2). We propose that PHF7 acts as a conserved epigenetic “reader” that activates the male germline sexual program.

show abstract

Section: Discussionmentioning

confidence: 64%

Phf7 Controls Male Sex Determination in the Drosophila Germline

2012

View full text Add to dashboard Cite

show abstract

“…RAG2 shares no transposase features with RAG1 and might not have been part of the original RAG transposon. RAG2 has a plant homeodomain, a feature shared with many chromatin-associated factors, and interacts with chromatin, particularly at histone H3 that is dimethylated or trimethylated at lysine 4 (H3K4me2 or H3K4me3, respectively)42–44. In developing lymphocytes, RAG2 binds a large number of regions of the genome with H3K4me3, whereas RAG1 specifically binds the immunoglobulin and TCR gene loci45.…”

Section: Adaptive Immunitymentioning

confidence: 99%

The origins of vertebrate adaptive immunity

2010

Self Cite

View full text Add to dashboard Cite

Adaptive immunity is mediated through numerous genetic and cellular processes that generate favourable somatic variants of antigen-binding receptors under evolutionary selection pressure by pathogens and other factors. Advances in our understanding of immunity in mammals and other model organisms are revealing the underlying basis and complexity of this remarkable system. Although the evolution of adaptive immunity has been considered to occur by acquisition of novel molecular capabilities, an increasing amount of information from new model systems suggest that co-option and redirection of preexisting systems are the major source of innovation. We combine evidence from a wide range of organisms to obtain an integrated view of the origins and patterns of divergence in adaptive immunity.With our increased understanding of mammalian adaptive immunity over the past decade, we have come to recognize the remarkable complexity of its underlying mechanisms. The core elements of this system are now mechanistically understood, such as DNA rearrangement, the generation of immune recognition diversity and the supporting cellular complexity that selects and expands cell populations expressing favourable antigen-binding receptor variants. General features of mammalian adaptive immunity -such as clonal selection, compartmental differentiation of lymphocytes, somatic hypermutation (SHM), allelic exclusion and a form of immunological memory -appeared before the emergence of the modern jawed vertebrates. Over the past several years, studies of immune receptors and immunity in a wide range of vertebrate and invertebrate species have revealed several similarities to present-day mammalian immunity and have provided insights into the evolutionary acquisition of immunological complexity 1,2 . We are within reach of important breakthroughs in our understanding of how adaptive immunity evolved in the context of an innate immune system and how these molecularly disparate systems are related and remain interdependent 3 . What has become increasingly clear is that the evolution of adaptive immunity requires the study of NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript a large range of molecular systems and that it cannot be understood from studies that are restricted to mice and humans or even from studies that use alternative vertebrate models, such as bony fish and sharks. Furthermore, we recognize that the complex set of processes that constitutes adaptive immunity can be addressed most effectively by examining its constituent steps; these include (not necessarily in order of evolutionary emergence or of equivalent complexity) the appearance of lymphocytes, the acquisition of antigen-binding receptor diversification mechanisms, the structural basis for recognition specificity, the evolution of mechanisms for receptor selection and the regulatory processes that target and attenuate immune responses. We are now in a better position to understand these essential steps in the evolutionary acquisition of ada...

show abstract

“…An important property of any protein that acts on chromosomal DNA is its ability to enter the nucleus of the cell, which is mediated by nuclear localization signals in vertebrate Rags. Similarly, both SpRag1L and SpRag2L are able to enter the nucleus when expressed in 293T cells [50]. Lastly, the vertebrate Rag complex is not only able to utilize naked double-stranded DNA substrates (in vitro or as transiently transfected plasmids), but also on the endogenous antigen receptor gene loci in the context of chromatin.…”

Section: Rag-like Genes In the Purple Sea Urchinmentioning

confidence: 99%

“…Lastly, the vertebrate Rag complex is not only able to utilize naked double-stranded DNA substrates (in vitro or as transiently transfected plasmids), but also on the endogenous antigen receptor gene loci in the context of chromatin. The PHD domain of vertebrate Rag2 plays an important role in this context as it binds to histone H3K4me3; this binding to histone tails is also a property of sea urchin Rag2 albeit with a slightly altered preference for the dimethylated H3K4me2 [50]. …”

Section: Rag-like Genes In the Purple Sea Urchinmentioning

confidence: 99%

The origins of the Rag genes—From transposition to V(D)J recombination

Fugmann

2010

Seminars in Immunology

Self Cite

View full text Add to dashboard Cite

The Recombination Activating Genes 1 and 2 (Rag1 and Rag2) encode the key enzyme that is required for the generation of the highly diversified antigen receptor repertoire central to adaptive immunity. The longstanding model proposed that this gene pair was acquired by horizontal gene transfer to explain its abrupt appearance in the vertebrate lineage. The analyses of the enormous amount of sequence data created by many genome sequencing projects now provides the basis for a more refined model as to how this unique gene pair evolved from a selfish DNA transposon into a sophisticated DNA recombinase essential for immunity. KeywordsRAG1; RAG2; transposase; evolution; adaptive immunity One hallmark of the adaptive immune system shared by all jawed vertebrates is a highly diversified repertoire of antigen receptors. These recognition molecules are encoded by the immunoglobulin (Ig) and T cell receptor (TCR) genes which are assembled from individual gene segments in a process named V(D)J recombination. This site-specific DNA recombination process is catalyzed by the proteins encoded by the recombination activating genes 1 and 2 (RAG1 and RAG2). This review will focus on the evolutionary origin of the Rag1/2 proteins, and how they evolved from a mobile DNA element into a sophisticated and tightly controlled DNA recombinase that is only active in lymphocytes. Cloning of the Rag genes -a historical overviewIn their germline configuration, the Ig and TCR gene loci consist of an array of individual V, D, and J gene segments and thus do not encode functional proteins. When this unique gene structure was discovered in 1976 by the Tonegawa lab, it immediately suggested that their assembly into functional antigen receptor genes requires an ordered DNA rearrangement process [reviewed in 1]. Further analyses revealed that each V, D, and J gene segment was flanked by conserved DNA sequence tags which were thought to mark these segments as building blocks and which served as substrates for a site-specific DNA recombinase [2]. Hence these tags were named recombination signal sequences (RSS), and found to occur in two

show abstract

The PHD domain of the sea urchin RAG2 homolog, SpRAG2L, recognizes dimethylated lysine 4 in histone H3 tails

Cited by 19 publications

References 40 publications

Phf7 Controls Male Sex Determination in the Drosophila Germline

Phf7 Controls Male Sex Determination in the Drosophila Germline

The origins of vertebrate adaptive immunity

The origins of the Rag genes—From transposition to V(D)J recombination

Contact Info

Product

Resources

About