Germline Transcription: A Key Regulator of Accessibility and Recombination

2009 ◽  
pp. 93-102 ◽  
Author(s):  
Iratxe Abarrategui ◽  
Michael S. Krangel
Keyword(s):  
Germline Transcription

scholarly journals H3K9me2 protects lifespan against the transgenerational burden of germline transcription in C. elegans

2019 ◽  
Author(s):  
Teresa W. Lee ◽  
Heidi S. David ◽  
Amanda K. Engstrom ◽  
Brandon S. Carpenter ◽  
David J. Katz
Keyword(s):  
Caenorhabditis Elegans ◽  
Histone H3 ◽  
Complex Trait ◽  
Wild Type ◽  
C Elegans ◽  
Germline Transcription ◽  
Active Transcription

ABSTRACTDuring active transcription, the COMPASS complex methylates histone H3 at lysine 4 (H3K4me). In Caenorhabditis elegans, mutations in COMPASS subunits, including WDR-5, extend lifespan and enable the inheritance of increased lifespan in wild-type descendants. Here we show that the increased lifespan of wdr-5 mutants is itself a transgenerational trait that manifests after eighteen generations and correlates with changes in the heterochromatin factor H3K9me2. Additionally, we find that wdr-5 mutant longevity and its inheritance requires the H3K9me2 methyltransferase MET-2 and can be recapitulated by a mutation in the putative H3K9me2 demethylase JHDM-1. These data suggest that lifespan is constrained by reduced H3K9me2 due to transcription-coupled H3K4me. wdr-5 mutants alleviate this burden, extending lifespan and enabling the inheritance of increased lifespan. Thus, H3K9me2 functions in the epigenetic establishment and inheritance of a complex trait. Based on this model, we propose that lifespan is limited by the germline in part because germline transcription reduces heterochromatin.

Promoter Element for Transcription of Unrearranged T-Cell Receptor β-Chain Gene in Pro-T Cells

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 3017-3025 ◽  
Author(s):  
Raymond T. Doty ◽  
Dong Xia ◽  
Suzanne P. Nguyen ◽  
Tanya R. Hathaway ◽  
Dennis M. Willerford
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
B Lymphocyte ◽  
Developmental Regulation ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Chain Gene ◽  
Germline Transcription ◽  
Lineage Specificity ◽  
T Cell Lines

Abstract The hallmark of T- and B-lymphocyte development is the rearrangement of variable (V), diversity (D), and joining (J) segments of T-cell receptor (TCR) and immunoglobulin (Ig) genes to generate a diverse repertoire of antigen receptor specificities in the immune system. The process of V(D)J recombination is shared in the rearrangement of all seven antigen receptor genes and is controlled by changes in chromatin structure, which regulate accessibility to the recombinase apparatus in a lineage- and stage-specific manner. These chromatin changes are linked to transcription of the locus in its unrearranged (germline) configuration. To understand how germline transcription of the TCRβ-chain gene is regulated, we determined the structure of germline transcripts initiating near the Dβ1 segment and identified a promoter within this region. The Dβ1 promoter is active in the presence of the TCRβ enhancer (Eβ), and in this context, exhibits preferential activity in pro-T versus mature T-cell lines, as well as T- versus B-lineage specificity. These studies provide insight into the developmental regulation of TCRβ germline transcription, one of the earliest steps in T-cell differentiation.

Analysis of γ4 Germline Transcription in Human B Cells

1999 ◽  
Vol 118 (2-4) ◽  
pp. 279-281 ◽  
Author(s):  
Alessandra Agresti ◽  
Donata Vercelli
Keyword(s):  
B Cells ◽  
Germline Transcription ◽  
Human B Cells

scholarly journals Localized Gene-Specific Induction of Accessibility to V(D)j Recombination Induced by E2a and Early B Cell Factor in Nonlymphoid Cells

2001 ◽  
Vol 194 (5) ◽  
pp. 645-656 ◽  
Author(s):  
Peter Goebel ◽  
Noel Janney ◽  
Joaquín R. Valenzuela ◽  
William J. Romanow ◽  
Cornelis Murre ◽  
...  
Keyword(s):  
B Cell ◽  
Ectopic Expression ◽  
Gene Families ◽  
Individual Gene ◽  
Germline Transcription ◽  
Specific Induction ◽  
Recombination Activating Gene ◽  
Direct Targeting ◽  
B Cell Precursors ◽  
Early B Cell Factor

Accessibility of immunoglobulin (Ig) gene segments to V(D)J recombination is highly regulated and is normally only achieved in B cell precursors. We previously showed that ectopic expression of E2A or early B cell factor (EBF) with recombination activating gene (RAG) induces rearrangement of IgH and IgL genes in nonlymphoid cells. VκI genes throughout the locus were induced to rearrange after transfection with E2A, suggesting that the entire Vκ locus was accessible. However, here we show that Ig loci are not opened globally but that recombination is localized. Gene families are interspersed in the DH, Vκ, and Vλ loci, and we show that certain families and individual genes undergo high levels of recombination after ectopic expression of E2A or EBF, while other families within the same locus are not induced to rearrange. Furthermore, in some families, induction of germline transcription correlates with the level of induced recombination, while in others there is no correlation, suggesting that recombination is not simply initiated by induction of germline transcription. The induced repertoire seen at 24 hours does not change significantly over time indicating the absence of many secondary rearrangements and also suggesting a direct targeting mechanism. We propose that accessibility occurs in a local manner, and that binding sites for factors facilitating accessibility are therefore likely to be associated with individual gene segments.

scholarly journals Immunoglobulin β Signaling Regulates Locus Accessibility for Ordered Immunoglobulin Gene Rearrangements

2000 ◽  
Vol 191 (8) ◽  
pp. 1333-1340 ◽  
Author(s):  
Kazushige Maki ◽  
Kisaburo Nagata ◽  
Fujiko Kitamura ◽  
Toshitada Takemori ◽  
Hajime Karasuyama
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Gene Rearrangement ◽  
Antigen Receptor ◽  
Cross Linking ◽  
Gene Rearrangements ◽  
B Cell Differentiation ◽  
Germline Transcription ◽  
Chain Locus ◽  
Bcr Signaling

The antigen receptor gene rearrangement at a given locus is tightly regulated with respect to cell lineage and developmental stage by an ill-defined mechanism. To study the possible role of precursor B cell antigen receptor (pre-BCR) signaling in the regulation of the ordered immunoglobulin (Ig) gene rearrangement during B cell differentiation, a newly developed system using μ heavy (H) chain membrane exon (μm)-deficient mice was employed. In this system, the antibody-mediated cross-linking of Igβ on developmentally arrested progenitor B (pro-B) cells mimicked pre-BCR signaling to induce early B cell differentiation in vivo. Analyses with ligation-mediated polymerase chain reaction revealed that the Igβ cross-linking induced the redirection of Ig gene rearrangements, namely, the suppression of ongoing rearrangements at the H chain locus and the activation of rearrangements at the light (L) chain locus. Upon the cross-linking, the κL chain germline transcription was found to be upregulated whereas the VH germline transcription was promptly downregulated. Notably, this alteration of the accessibility at the H and L chain loci was detected even before the induction of cellular differentiation became detectable by the change of surface phenotype. Thus, the pre-BCR signaling through Igβ appears to regulate the ordered Ig gene rearrangement by altering the Ig locus accessibility.

scholarly journals Biallelic Germline Transcription at the κ Immunoglobulin Locus

2003 ◽  
Vol 197 (6) ◽  
pp. 743-750 ◽  
Author(s):  
Nandita Singh ◽  
Yehudit Bergman ◽  
Howard Cedar ◽  
Andrew Chess
Keyword(s):  
B Cells ◽  
Chromatin Structure ◽  
Replication Timing ◽  
Allelic Exclusion ◽  
Antigen Receptors ◽  
Germline Transcription ◽  
Immature B Cells ◽  
Recombination Activating Gene ◽  
Immunoglobulin Locus

Rearrangement of antigen receptor genes generates a vast array of antigen receptors on lymphocytes. The establishment of allelic exclusion in immunoglobulin genes requires differential treatment of the two sequence identical alleles. In the case of the κ immunoglobulin locus, changes in chromatin structure, methylation, and replication timing of the two alleles are all potentially involved in regulating rearrangement. Additionally, germline transcription of the κ locus which precedes rearrangement has been proposed to reflect an opening of the chromatin structure rendering it available for rearrangement. As the initial restriction of rearrangement to one allele is critical to the establishment of allelic exclusion, a key question is whether or not germline transcription at the κ locus is monoallelic or biallelic. We have used a sensitive reverse transcription-polymerase chain reaction (RT-PCR) assay and an RNA–fluorescence in situ hybridization (FISH) to show that germline transcription of the κ locus is biallelic in wild-type immature B cells and in recombination activating gene (RAG)−/−, μ+ B cells. Therefore, germline transcription is unlikely to dictate which allele will be rearranged first and rather reflects a general opening on both alleles that must be accompanied by a mechanism allowing one of the two alleles to be rearranged first.

scholarly journals Tannic acid, a higher galloylated pentagalloylglucose, suppresses antigen-specific IgE production by inhibiting ɛ germline transcription induced by STAT6 activation

FEBS Open Bio ◽  
2013 ◽  
Vol 3 (1) ◽  
pp. 341-345 ◽  
Author(s):  
Yoon Hee Kim ◽  
Miki Yoshimoto ◽  
Kazuko Nakayama ◽  
Sousuke Tanino ◽  
Yoshinori Fujimura ◽  
...  
Keyword(s):  
Tannic Acid ◽  
Specific Ige ◽  
Germline Transcription

Regulation of ϵ germline transcription and switch region mutations by IgH locus 3′ enhancers in transgenic mice

Blood ◽  
2006 ◽  
Vol 109 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Jurga Laurencikiene ◽  
Vytas Tamosiunas ◽  
Eva Severinson
Keyword(s):  
B Cells ◽  
Cytidine Deaminase ◽  
Switch Region ◽  
Endogenous Gene ◽  
Class Switch ◽  
Germline Transcription ◽  
Igh Locus ◽  
Activation Induced Cytidine Deaminase ◽  
Switch Regions ◽  
Transgenic Lines

Abstract Germline (GL) transcription is regulated by specific promoters and immunoglobulin heavy chain (IgH) 3′ locus enhancers and is necessary for Ig class-switch recombination (CSR). We have generated different transgenic lines containing the GL ϵ promoter, switch (S) ϵ region, and constant (C) ϵ region with or without the DNase I–sensitive regions (HS) 3A-HS1,2 or HS3B-HS4 3′ IgH enhancer pairs. The enhancerless construct was expressed in B cells activated by interleukin (IL)–4 and CD40, thus resembling regulation of the endogenous gene. Both enhancer-containing transgenes efficiently increased expression in B cells and were strongly up-regulated by stimuli. In addition, Sϵ regions of the transgene containing HS3B-HS4 were mutated in activated, sorted B cells. Such mutations are known to precede CSR and are dependent on activation-induced cytidine deaminase (AID). Our findings show that all elements necessary for recruitment of the recombination machinery are present in the transgene containing HS3 and HS4. These enhancers probably provide something more specific than mere increased accessibility of switch regions. We propose that transcription factors binding the enhancers help to target the recombination machinery to the switch regions.

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