Histone 3 lysine 4 methylation during the pre-B to immature B-cell transition

Perkins, Eric J.; Kee, Barbara L.; Ramsden, Dale A.

doi:10.1093/nar/gkh523

Cited by 33 publications

(33 citation statements)

References 35 publications

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“…In such cell lines, which have been used by several groups as models for pre-B cell differentiation (12,(31)(32)(33) the changes in Ig locus accessibility with differentiation events in 103X7 cells, we verified the timing of transcription and recombination events after temperature shift. RT-PCR revealed that rag1 and rag2 transcripts increased within 2 h of temperature shift, while transcripts for the components of the surrogate LC, 5, and Vpre-B were present before the temperature shift (Fig.…”

Section: Differentiation Events In 103x7 and Pre-b Cellsmentioning

confidence: 85%

“…Several investigators (3,12) have examined the chromatin histone modifications of several locations in the Ig locus between J4 and the E3Ј. A chromatin immunoprecipitation (ChIP) analysis in a ts Abelson-transformed pre-B cell line demonstrated that activation of the Ig locus was associated with increased H3K4 methylation over the region of the Ig germline transcript on the recombining allele (12).…”

mentioning

confidence: 99%

“…A chromatin immunoprecipitation (ChIP) analysis in a ts Abelson-transformed pre-B cell line demonstrated that activation of the Ig locus was associated with increased H3K4 methylation over the region of the Ig germline transcript on the recombining allele (12). Other experiments (3) showed increased enrichments of AcH3 and H3K4 methylation on the allele that was not associated with heterochromatin in developing B cells.…”

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confidence: 99%

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Dynamic Changes in Accessibility, Nuclear Positioning, Recombination, and Transcription at the Igκ Locus

Fitzsimmons

Bernstein

Max

et al. 2007

The Journal of Immunology

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The 3-megabase Igκ locus undergoes differentially controlled nuclear positioning events and chromatin structural changes during the course of B cell development. The temporal association of chromatin structural changes, transcription, and recombination at the Igκ locus was determined in a murine pre-B cell line that can be induced to recombine at the Igκ locus and in ex vivo-cultured murine pre-B cells. Additionally, the timing of nuclear positioning relative to the temporal order of chromatin structural changes and recombination and transcription was determined. We demonstrate that before induction, the Igκ locus was poised for recombination; both alleles were in a contracted state, and the enrichment of histone modifications and germline transcripts of specific Vκ genes were observed. Histone modifications of the Vκ genes did not vary upon induction but the levels of modifications correlated with the levels of germline Vκ gene transcripts and recombination. Upon induction, but before VκJκ recombination, centromeric recruitment of single Igκ alleles occurred. DNase I sensitivity of the entire locus increased gradually over the course of differentiation while the enrichment of histone modifications downstream of the Vκ genes was increased in the silencer regions upstream of Jκ1, within the Igκ sterile transcript, the κ constant region, the Eκi and Eκ3′ enhancers, and the recombining sequence. The ex vivo pre-B cells showed similar patterns of histone modifications across the locus except at the Vκ genes. In this study, H3 acetylation correlated with levels of germline transcripts while H3 methylation correlated with levels of recombination.

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Section: Differentiation Events In 103x7 and Pre-b Cellsmentioning

confidence: 85%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dynamic Changes in Accessibility, Nuclear Positioning, Recombination, and Transcription at the Igκ Locus

Fitzsimmons

Bernstein

Max

et al. 2007

The Journal of Immunology

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“…These can be categorized as "writers" (adding modifications), "erasers" (removing such modification), or "readers" (recognizing such modifications) [ 21 ]. One chromatin mark that correlates well with accessible areas in antigen receptor gene loci is hypermethylation of H3K4 [ 24,27,[35][36][37]. Recently, strong experimental evidence was provided that the RAG2 PHD domain is a histone code reader, rendering the recombinase highly active when in contact with nucleosomes displaying H3K4me3 [ 24,27 ].…”

Section: Discussionmentioning

confidence: 99%

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

Wilson

Norton

Fugmann

2008

Developmental & Comparative Immunology

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V(D)J recombination is a somatic gene rearrangement process that assembles antigen receptor genes from individual segments during lymphocyte development. The access of the RAG1/RAG2 recombinase to these gene segments is regulated at the level of chromatin modifications, in particular histone tail modifications. Trimethylation of lysine 4 in histone H3 (H3K4me3) correlates with actively recombining gene elements, and this mark is recognized and interpreted by the plant homeodomain (PHD) of RAG2. Here we report that the PHD domain of the only known invertebrate homolog of RAG2, the SpRAG2L protein of the purple sea urchin (Strongylocentrotus purpuratus) also binds to methylated histones, but with a unique preference for H3K4me2. While the cognate substrate for the sea urchin RAG1L/RAG2L complex remains elusive, the affinity for histone tails and the nuclear localization of ectopically expressed SpRAG2L strongly support the model that this enzyme complex exerts its activity on DNA in the context of chromatin.

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“…RAG2 binds even more tightly when the nucleosome is symmetrically dimethylated on arginine 2 of histone H3 (H3R2me2s) in addition to bearing the H3K4me3 modification (28). H3K4me3 and H3R2me2s are found at recombinationally accessible antigen receptor loci, such as the IgH D and J segments in pro-B cells, Igκ in pre-B cells, and TCRα in pro-T cells (26,(29)(30)(31). Recognition of H3K4me3 by RAG2-PHD is required for efficient V(D)J recombination in vivo (26,27).…”

Section: Significancementioning

confidence: 99%

Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination

Pulivarthy

Lion

Kuzu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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We show that the physical distribution of nucleosomes at antigen receptor loci is subject to regulated cell type-specific and lineagespecific positioning and correlates with the accessibility of these gene segments to recombination. At the Ig heavy chain locus (IgH), a nucleosome in pro-B cells is generally positioned over each IgH variable (VH) coding segment, directly adjacent to the recombination signal sequence (RSS), placing the RSS in a position accessible to the recombination activating gene (RAG) recombinase. These changes result in establishment of a specific chromatin organization at the RSS that facilitates accessibility of the genomic DNA for the RAG recombinase. In contrast, in mouse embryonic fibroblasts the coding segment is depleted of nucleosomes, which instead cover the RSS, thereby rendering it inaccessible. Pro-T cells exhibit a pattern intermediate between pro-B cells and mouse embryonic fibroblasts. We also find large-scale variations of nucleosome density over hundreds of kilobases, delineating chromosomal domains within IgH, in a cell typedependent manner. These findings suggest that developmentally regulated changes in nucleosome location and occupancy, in addition to the known chromatin modifications, play a fundamental role in regulating V(D)J recombination. Nucleosome positioning-which has previously been observed to vary locally at individual enhancers and promoters-may be a more general mechanism by which cells can regulate the accessibility of the genome during development, at scales ranging from several hundred base pairs to many kilobases.T he diverse repertoire of antigen receptors in vertebrates is generated by an ordered series of somatic site-specific DNA rearrangement events, collectively termed V(D)J recombination. Antigen receptor genes are assembled from V, D, and J gene segments organized into seven different loci [T-cell receptor (TCR) α, β, γ, and δ, and Ig H, κ, and λ], each of which undergoes a series of recombination reactions to generate a functional TCR or B-cell receptor (BCR) (1, 2) Rearrangement is lineage-specific, such that BCR genes are fully rearranged only in B cells and TCR genes are assembled only in T cells. Rearrangement also occurs in a preferred temporal order. For example, at the human and murine IgH loci, joining of D to J segments precedes V to DJ joining, and IgH joining precedes joining at Igκ (or Igλ) (3). In addition, recombination at several loci shows "allelic exclusion": Functional VDJH or VJκ/Jλ joining occurs only on one allele (4).Recombination is initiated by the lymphocyte-specific recombination activating gene (RAG)1/RAG2 endonuclease. RAG1/2 cleaves at the recombination signal sequences (RSSs) flanking all antigen receptor gene segments. The consensus RSS consists of a heptamer sequence directly adjacent to the coding element and an A/T-rich nonamer separated from the heptamer by a spacer region of conserved length (12 or 23 bp) but relatively nonconserved sequence. The broken ends are then joined with the aid of DNA repair proteins,...

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Histone 3 lysine 4 methylation during the pre-B to immature B-cell transition

Cited by 33 publications

References 35 publications

Dynamic Changes in Accessibility, Nuclear Positioning, Recombination, and Transcription at the Igκ Locus

Dynamic Changes in Accessibility, Nuclear Positioning, Recombination, and Transcription at the Igκ Locus

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

Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination

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