Nuclear organisation and gene expression

Baxter, Jonathan; Merkenschlager, Matthias; Fisher, Amanda G.

doi:10.1016/s0955-0674(02)00339-3

Cited by 51 publications

(30 citation statements)

References 52 publications

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“…Several groups showed that before undergoing rearrangement, the IgH locus moves from its default position at the nuclear periphery to a more central compartment (Fuxa et al, 2004;Kosak et al, 2002), going along with the observation that the nuclear periphery has a repressive effect on transcription (Andrulis et al, 1998;Baxter et al, 2002;Reddy et al, 2008) and, therefore, might keep the IgH locus in an inaccessible state. These observations are consistent with the peripheral location of the IgH locus in thymocytes which have only low level of D to J H and no V H to DJ H rearrangements (Fuxa et al, 2004;Kosak et al, 2002;Kurosawa et al, 1981).…”

Section: Spatial Organization and Nuclear Positioning Of The Igh Locusmentioning

confidence: 88%

Chapter 1 Cis‐Regulatory Elements and Epigenetic Changes Control Genomic Rearrangements of the IgH Locus

Perlot

Alt

2008

Advances in Immunology

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Immunoglobulin variable region exons are assembled from discontinuous variable (V), diversity (D), and joining (J) segments by the process of V(D)J recombination. V(D)J rearrangements of the immunoglobulin heavy chain (IgH) locus are tightly controlled in a tissue-specific, ordered and allele-specific manner by regulating accessibility of V, D, and J segments to the recombination activating gene proteins which are the specific components of the V(D)J recombinase. In this review we discuss recent advances and established models brought forward to explain the mechanisms underlying accessibility control of V(D)J recombination, including research on germline transcripts, spatial organization, and chromatin modifications of the immunoglobulin heavy chain (IgH) locus. Furthermore, we review the functions of well-described and potential new cis-regulatory elements with regard to processes such as V(D)J recombination, allelic exclusion, and IgH class switch recombination.

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Section: Spatial Organization and Nuclear Positioning Of The Igh Locusmentioning

confidence: 88%

Chapter 1 Cis‐Regulatory Elements and Epigenetic Changes Control Genomic Rearrangements of the IgH Locus

Perlot

Alt

2008

Advances in Immunology

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“…As illustrated by the two-step model in Figure 7D, the IgH locus is anchored via the distal V H genes at the nuclear periphery and is oriented in its extended chromatin state toward the center of the nucleus in all non-B cells such as pro-T cells. In this default configuration of the IgH locus, the distal V H genes are likely to be silenced, as the nuclear periphery may function as a repressive compartment in higher eukaryotes in analogy to yeast (Baxter et al 2002;Hediger and Gasser 2002). The more centrally located, proximal IgH domain may, however, be accessible for the V(D)J recombinase, which could account for the low level of D H -J H rearrangements observed in thymocytes and dendritic cells (Kurosawa et al 1981;Corcoran et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Both IgH alleles are present in an extended chromatin configuration at the nuclear periphery of non-B-lymphoid cells, whereas they are relocated to central positions of the nucleus and undergo large-scale contraction in committed pro-B cells (Kosak et al 2002). Subnuclear compartmentalization was thus proposed as a novel mechanism for regulating IgH transcription and recombination during B-cell development (Kosak et al 2002), particularly because the nuclear periphery in higher eukaryotes may function as a repressive compartment for transcriptional silencing (Baxter et al 2002) in analogy to yeast (Hediger and Gasser 2002).…”

mentioning

confidence: 99%

Pax5 inducesV-to-DJrearrangements and locus contraction of theimmunoglobulin heavy-chaingene

Fuxa¹,

Skok²,

Souabni³

et al. 2004

Genes Dev.

378

457

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“…Chromatin in the interphase nucleus is highly organized into discrete chromosome territories (1,2), and the position of a particular genetic locus both within a chromosome territory and within the nucleus can influence its transcriptional state (3,4). In the yeast Saccharomyces cerevisiae, specific genetic loci physically relocalize from the nuclear interior to the nuclear periphery upon transcriptional activation (5-10).…”

mentioning

confidence: 99%

Actively Transcribed GAL Genes Can Be Physically Linked to the Nuclear Pore by the SAGA Chromatin Modifying Complex

Luthra

Kerr

Harreman

et al. 2007

Journal of Biological Chemistry

120

112

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Recent work has demonstrated that some actively transcribed genes closely associate with nuclear pore complexes (NPC) at the nuclear periphery. The Saccharomyces cerevisiae Mlp1 and Mlp2 proteins are components of the inner nuclear basket of the nuclear pore that mediate interactions with these active genes. To investigate the physical link between the NPC and active loci, we identified proteins that interact with the carboxyl-terminal globular domain of Mlp1 by tandem affinity purification coupled with mass spectrometry. This analysis led to the identification of several components of the Spt-Ada-Gcn5-acetyltransferase (SAGA) histone acetyltransferase complex, Gcn5, Ada2, and Spt7. We utilized co-immunoprecipitation and in vitro binding assays to confirm the interaction between the Mlp proteins and SAGA components. Chromatin immunoprecipitation experiments revealed that Mlp1 and SAGA components associate with the same region of the GAL promoters. Critically, this Mlp-promoter interaction depends on the integrity of the SAGA complex. These results identify a physical association between SAGA and the NPC, and support previous results that relied upon visualization of GAL loci at the nuclear periphery by microscopy (Cabal, G. G. Genovesio, A., Rodriguez-Navarro, S., Zimmer, C., Gadal, O., Lesne, A., Buc, H., Feuerbach-Fournier, F., Olivo-Marin, J.-C., Hurt, E. C., and Nehrbass, U. (2006) Nature 441, 770 -773). We propose that a physical interaction between nuclear pore components and the SAGA complex can link the actively transcribed GAL genes to the nuclear pore.

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Nuclear organisation and gene expression

Cited by 51 publications

References 52 publications

Chapter 1 Cis‐Regulatory Elements and Epigenetic Changes Control Genomic Rearrangements of the IgH Locus

Chapter 1 Cis‐Regulatory Elements and Epigenetic Changes Control Genomic Rearrangements of the IgH Locus

Pax5 inducesV-to-DJrearrangements and locus contraction of theimmunoglobulin heavy-chaingene

Actively Transcribed GAL Genes Can Be Physically Linked to the Nuclear Pore by the SAGA Chromatin Modifying Complex

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