Chromatin Remodeling at the Ig Loci Prior to V(D)J Recombination

Maës, Jérôme; O’Neill, Laura P.; Cavelier, Patricia; Turner, Bryan M.; Rougeon, François; Goodhardt, Michèle

doi:10.4049/jimmunol.167.2.866

Cited by 98 publications

(91 citation statements)

References 60 publications

(69 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, an ϳ1-Mb region covering the distal V H genes is required for Igh locus association with the nuclear periphery (42). Transient loss of this association appears essential to V to DJ rearrangements involving the distal V H genes, but the Igh locus reforms its attachment to the nuclear lamina in B cells and Ig-secreting cells (43)(44)(45)(46). The effect of this association on Ig transcription is not yet clear.…”

Section: Discussionmentioning

confidence: 99%

Transcription of a Productively Rearranged Ig VDJCα Does Not Require the Presence of HS4 in the Igh 3′ Regulatory Region

Zhang

Alaie-Petrillo

Kon

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

V gene assembly, class switch recombination, and somatic hypermutation are gene-modifying processes essential to the development of an effective Ab response. If inappropriately applied, however, these processes can mediate genetic changes that lead to disease (e.g., lymphoma). A series of control elements within the Ig H chain (Igh) locus has been implicated in regulating these processes as well as in regulating IgH gene transcription. These include the intronic enhancer (Eμ) and several elements at the 3′ end of the locus (hs1,2, hs3a, hs3b, and hs4) known collectively as the 3′ regulatory region. Although it is clear that the Eμ plays a unique role in V gene assembly, it has not been established whether there are unique functions for each element within the 3′ regulatory region. In earlier studies in mice and in mouse cell lines, pairwise deletion of hs3b and hs4 had a dramatic effect on both class switch recombination and IgH gene transcription; deletion of an element almost identical with hs3b (hs3a), however, yielded no discernible phenotype. To test the resulting hypothesis that hs4 is uniquely required for these processes, we induced the deletion of hs4 within a bacterial artificial chromosome transgene designed to closely approximate the 3′ end of the natural Igh locus. When introduced into an Ig-secreting cell line, an Igα transcription unit within the bacterial artificial chromosome was expressed efficiently and the subsequent deletion of hs4 only moderately affected Igα expression. Thus, hs4 does not play a uniquely essential role in the transcription of a productively rearranged Ig VDJCα transcription unit.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcription of a Productively Rearranged Ig VDJCα Does Not Require the Presence of HS4 in the Igh 3′ Regulatory Region

Zhang

Alaie-Petrillo

Kon

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Evaluation of the chromatin structure of multipotent hematopoietic cells indicated that the lineage-associated genes, globin, myeloperoxidase, immunoglobulin H (IgH), and CD3␦ have accessible control regions before unilineage commitment. [55][56][57][58][59] Other work indicates that chromatin remodeling factors may be recruited in one phase of the cell cycle for ultimate action in a later phase, which in turn results in changes in transcriptional programs. Consistent with the model of a fluctuating cell cycle-based stem cell phenotype and asymmetric division is the proposal of McConnell and Kaznowski 60 that cell cycle passage could determine the fate of cells derived from stem cell division and renew stem cell multipotency.…”

Section: Cell Cycle Transit and Chromatin Modulationmentioning

confidence: 99%

“…In previous studies chromatin modulation at the B-globin and lysozyme gene loci were evaluated [54][55][56][57] and myeloid specific cis-regulatory elements showed a specific chromatin pattern at the lysozyme locus in myelomonocytic cells at different differentiation stages. This chromatin pattern was also found in multipotent hematopoietic progenitors, but it disappeared when cells differentiated into the erythroid lineage.…”

Section: Cell Cycle Transit and Chromatin Modulationmentioning

confidence: 99%

The chiaroscuro stem cell: a unified stem cell theory

Quesenberry

Colvin

Lambert

2002

Blood

119

View full text Add to dashboard Cite

Hematopoiesis has been considered hierarchical in nature, but recent data suggest that the system is not hierarchical and is, in fact, quite functionally plastic. Existing data indicate that engraftment and progenitor phenotypes vary inversely with cell cycle transit and that gene expression also varies widely. These observations suggest that there is no progenitor/stem cell hierarchy, but rather a reversible continuum. This may, in turn, be dependent on shifting chromatin and gene expression with cell cycle transit. If the phenotype of these primitive marrow cells changes from engraftable stem cell to progenitor and back to engraftable stem cell with cycle transit, then this suggests that the identity of the engraftable stem cell may be partially masked in nonsynchronized marrow cell popula- IntroductionWe present here a different view of early hematopoiesis. This is not the standard dogma of many investigators in the field, but is built upon solid work by many laboratories over many years. This is a perspective, and thus naturally reflects the biases of the authors. These, in turn, have a basis in many published studies from our laboratory and other laboratories and also from extensive unpublished, but abstracted, data from our laboratory. It is appropriate to consider this contribution as speculative in nature.The term chiaroscuro refers to the treatment of light and shade in painting. Our current view of the changing phenotype of the marrow stem cell suggests a chiaroscuro nature to this picture.In general, models of stem cell regulation have been hierarchical. 1,2 A primitive stem cell, with great potential, gives rise to a proliferating progenitor pool, which in turn gives rise to recognizable differentiated cells. During this process, proliferative potential is lost, while specific differentiated features are acquired. Presumptively, but without definite proof, there is also self-renewal at the most primitive stem cell level, and this is also lost with differentiation. Many data exist to support such a hierarchical model. Marrow cells have been separated with short-and long-term repopulation potential 3,4 and progenitors have been characterized as exclusively committed to the production of restricted progeny. 5,6 In addition, the clear expansion of different progenitor types in cytokinestimulated in vitro culture with a loss of long-term engraftment capacity speaks to the existence of a progenitor hierarchy, at least at the more differentiated progenitor levels. 7,8 A model encompassing these features is shown in Figure 1.This model does not fit with all published data. For instance, the "daughter cell" or paired-progenitor experiments of Suda and colleagues 9 indicate that a primitive progenitor cell can make totally different lineage choices during one cell cycle transit, such that, for example, one daughter cell forms an erythroid colony while the other daughter (or sister) cell forms a neutrophilmacrophage colony. Out of a total of 387 pairs evaluated, 68 pairs of colonies consisted of dissimilar com...

show abstract

“…DNase I analysis has shown that initiation of V(D)J recombination at the Ig loci is preceded by increased nuclease sensitivity and changes in chromatin structure (Maës et al, 2001). Furthermore, it has been demonstrated that demethylation of L chain genes occurs during B cell development, and is associated with onset of V(D)J recombination (Goodhardt et al, 1993;Mostoslavsky et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Chromatin accessibility and epigenetic modifications differ between frequently and infrequently rearranging VH genes

Espinoza

Feeney

2007

Molecular Immunology

View full text Add to dashboard Cite

The molecular mechanisms that control the temporal and lineage-specific accessibility, as well as the rearrangement frequency of V H genes for V H -to-DJ H recombination, are not fully understood. We previously found a positive correlation between the extent of histone acetylation and the differential rearrangement frequency of individual V H genes. Here, we demonstrated that poorly rearranging V H genes are more highly associated with histone H3 dimethylated at lysine 9, a marker of repressive chromatin, than frequently rearranging V H genes. We also observed a positive relationship between the differential binding of Pax5 to individual V H S107 genes and rearrangement frequency. Furthermore, we showed that accessibility of the regions flanking the Pax5 binding site and the RSS to restriction enzyme cleavage correspond with the differential rearrangement frequency of the V H S107 family members. In addition, we found that the CpG sites located in the coding regions of V H genes are methylated in general, while the extent of DNA methylation drops dramatically near the RSS. For the V H S107 family, one CpG site located 101 bp upstream of the RSS showed variable methylation that correlates with rearrangement frequency, and the methylation status of a CpG site located 34 bp downstream of the RSS could also favor the rearrangement of V1 over V11. These findings suggest that the extent of histone modifications, chromatin accessibility, DNA methylation, as well as the differential binding of Pax5 to V H coding regions, could all influence the rearrangement frequency of individual V H genes, although some of these mechanisms are not strictly B cell specific.

show abstract

Chromatin Remodeling at the Ig Loci Prior to V(D)J Recombination

Cited by 98 publications

References 60 publications

Transcription of a Productively Rearranged Ig VDJCα Does Not Require the Presence of HS4 in the Igh 3′ Regulatory Region

Transcription of a Productively Rearranged Ig VDJCα Does Not Require the Presence of HS4 in the Igh 3′ Regulatory Region

The chiaroscuro stem cell: a unified stem cell theory

Chromatin accessibility and epigenetic modifications differ between frequently and infrequently rearranging VH genes

Contact Info

Product

Resources

About