Dataset Information

Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4.

ABSTRACT: In the earliest stages of antigen receptor assembly, D and J segments of the Ig heavy chain and T cell receptor beta loci are recombined in B and T cells, respectively, whereas the V segments are not. Distinct distribution patterns of various histone modifications and the nucleosome-remodeling factor BRG1 are found at "active" (DJ) and "inactive" (V) regions. Striking "hotspots" of histone H3 dimethylated at lysine 4 (di-Me H3-K4) are localized at the ends of the active DJ domains of both the Ig heavy chain and T cell receptor beta loci. BRG1 is not localized to specific sequences, as it is with transcriptional initiation, but rather associates with the entire active locus in a pattern that mirrors acetylation of histone H3. Within some inactive loci marked by H3-K9 dimethylation, two distinct levels of methylation are found in a nonrandom gene-segment-specific pattern. We suggest that the hotspots of di-Me H3-K4 are important marks for locus accessibility. The specific patterns of modification imply that the regulation of V(D)J recombination involves recruitment of specific methyltransferases in a localized manner.

SUBMITTER: Morshead KB

PROVIDER: S-EPMC208800 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4.

Morshead Katrina B KB Ciccone David N DN Taverna Sean D SD Allis C David CD Oettinger Marjorie A MA

Proceedings of the National Academy of Sciences of the United States of America 20030919 20

In the earliest stages of antigen receptor assembly, D and J segments of the Ig heavy chain and T cell receptor beta loci are recombined in B and T cells, respectively, whereas the V segments are not. Distinct distribution patterns of various histone modifications and the nucleosome-remodeling factor BRG1 are found at "active" (DJ) and "inactive" (V) regions. Striking "hotspots" of histone H3 dimethylated at lysine 4 (di-Me H3-K4) are localized at the ends of the active DJ domains of both the Ig ...[more]

PMID: 14500909

Similar Datasets

Project description:The loss of genome stability is an early event that drives the development and progression of virtually all tumor types. Recent studies have revealed that certain histone post-translational modifications exhibit dynamic and global increases in abundance that coincide with mitosis and exhibit essential roles in maintaining genomic stability. Histone H2B ubiquitination at lysine 120 (H2Bub1) is regulated by RNF20, an E3 ubiquitin ligase that is altered in many tumor types. Through an evolutionarily conserved trans-histone pathway, H2Bub1 is an essential prerequisite for subsequent downstream dimethylation events at lysines 4 (H3K4me2) and 79 (H3K79me2) of histone H3. Although the role that RNF20 plays in tumorigenesis has garnered much attention, the downstream components of the trans-histone pathway, H3K4me2 and H3K79me2, and their potential contributions to genome stability remain largely overlooked. In this study, we employ single-cell imaging and biochemical approaches to investigate the spatial and temporal patterning of RNF20, H2Bub1, H3K4me2, and H3K79me2 throughout the cell cycle, with a particular focus on mitosis. We show that H2Bub1, H3K4me2, and H3K79me2 exhibit distinct temporal progression patterns throughout the cell cycle. Most notably, we demonstrate that H3K79me2 is a highly dynamic histone post-translational modification that reaches maximal abundance during mitosis in an H2Bub1-independent manner. Using RNAi and chemical genetic approaches, we identify DOT1L as a histone methyltransferase required for the mitotic-associated increases in H3K79me2. We also demonstrate that the loss of mitotic H3K79me2 levels correlates with increases in chromosome numbers and increases in mitotic defects. Collectively, these data suggest that H3K79me2 dynamics during mitosis are normally required to maintain genome stability and further implicate the loss of H3K79me2 during mitosis as a pathogenic event that contributes to the development and progression of tumors.

Project description:BackgroundHistone H3 lysine 4 tri-methylation (H3K4me3) and histone H3 lysine 9 tri-methylation (H3K9me3) are widely perceived to be opposing and often mutually exclusive chromatin modifications. However, both are needed for certain light-activated genes in Neurospora crassa (Neurospora), including frequency (frq) and vivid (vvd). Except for these 2 loci, little is known about how H3K4me3 and H3K9me3 impact and contribute to light-regulated gene expression.ResultsIn this report, we performed a multi-dimensional genomic analysis to understand the role of H3K4me3 and H3K9me3 using the Neurospora light response as the system. RNA-seq on strains lacking H3 lysine 4 methyltransferase (KMT2/SET-1) and histone H3 lysine 9 methyltransferase (KMT1/DIM-5) revealed some light-activated genes had altered expression, but the light response was largely intact. Comparing these 2 mutants to wild-type (WT), we found that roughly equal numbers of genes showed elevated and reduced expression in the dark and the light making the environmental stimulus somewhat ancillary to the genome-wide effects. ChIP-seq experiments revealed H3K4me3 and H3K9me3 had only minor changes in response to light in WT, but there were notable alterations in H3K4me3 in Δkmt1/Δdim-5 and H3K9me3 in Δkmt2/Δset-1 indicating crosstalk and redistribution between the modifications. Integrated analysis of the RNA-seq and ChIP-seq highlighted context-dependent roles for KMT2/SET1 and KMT1/DIM-5 as either co-activators or co-repressors with some overlap as co-regulators. At a small subset of loci, H3K4 methylation is required for H3K9me3-mediated facultative heterochromatin including, the central clock gene frequency (frq). Finally, we used sequential ChIP (re-ChIP) experiment to confirm Neurospora contains K4/K9 bivalent domains.ConclusionsCollectively, these data indicate there are obfuscated regulatory roles for H3K4 methylation and H3K9 methylation depending on genome location with some minor overlap and co-dependency.

Dataset Information

Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4.

Publications

Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets