A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.

Scheuermann, Richard H.; Chen, Una

doi:10.1101/gad.3.8.1255

Cited by 108 publications

(92 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because CDP has a stronger affinity for these sites than the activator protein, binding of CDP prevents binding of the activator, thus leading to repression of gene expression. Although most of these activators are not known, recent results suggest that immunoglobulin heavy-chain transcription may be, in part, restricted to B cells through the binding of B-cell-specific activators, such as Bright (30), that accompany the decreasing levels of CDP repressor present during B-cell differentiation (56). The identities of activators that bind to MMTV LTR sites occupied by CDP during mammary gland differentiation are unknown.…”

Section: Fig 8 Stable Transfections Of Mmtv Ltr-reporter Gene Constmentioning

confidence: 99%

“…However, it is an attractive possibility that CDP binding sites could be used to isolate proteins that activate transcription following the loss of CDP binding activity that accompanies differentiation of the mammary gland. Because the loss of CDP occurs in a number of differentiating cell types (1,56,57), this strategy also may be applicable to the isolation of transcriptional activators in other tissues.…”

Section: Fig 8 Stable Transfections Of Mmtv Ltr-reporter Gene Constmentioning

confidence: 99%

See 1 more Smart Citation

CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

Zhu

Gregg

Lozano

et al. 2000

J Virol

View full text Add to dashboard Cite

show abstract

Section: Fig 8 Stable Transfections Of Mmtv Ltr-reporter Gene Constmentioning

confidence: 99%

Section: Fig 8 Stable Transfections Of Mmtv Ltr-reporter Gene Constmentioning

confidence: 99%

CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

Zhu

Gregg

Lozano

et al. 2000

J Virol

View full text Add to dashboard Cite

show abstract

“…In the IgH locus, the intronic E enhancer is flanked on both sides by intimately associated MARs (24). In B cells, they are associated with MAR-BP1 and Bright (39,52), whereas in non-B cells they are bound by SATB1 and NF-NR which is likely Cux/CDP (28,53). 3 Similarly, MAR ␤ is just 400 bp upstream of E ␤ and is also associated with Cux/CDP and SATB1.…”

Section: Figmentioning

confidence: 99%

“…In the immunoglobulin heavy chain (IgH) locus, MARs flank the intronic enhancer E and are in close proximity to V H promoters (22)(23)(24)(25)(26). Reporter gene assays in cell lines and transgenic mice have suggested that these MARs exert both positive and negative effects on IgH gene transcription and promote long range chromatin accessibility (27)(28)(29)(30)(31). A highly conserved MAR is also found 200 base pairs (bp) upstream of the intronic immunoglobulin (Ig) enhancer in mouse, human, and rabbit (22,32).…”

Section: Cd8mentioning

confidence: 99%

A Nuclear Matrix Attachment Region Upstream of the T Cell Receptor β Gene Enhancer Binds Cux/CDP and SATB1 and Modulates Enhancer-dependent Reporter Gene Expression but Not Endogenous Gene Expression

Chattopadhyay

Whitehurst

Chen

1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

We have previously identified a DNase I-hypersensitive site in the T cell receptor ␤ locus, designated HS1, that is located 400 base pairs upstream of the transcriptional enhancer E ␤ and is induced during CD4 ؊ CD8 ؊ to CD4 ؉ CD8؉ thymocyte differentiation. Using electrophoretic mobility shift assays, we show that HS1 induction correlates with increased binding of two nuclear factors, Cux/CDP and SATB1, to a 170-base pair DNA sequence within HS1. Furthermore, we demonstrate that HS1 is a nuclear matrix attachment region, referred to as MAR ␤ . These findings demonstrate that an analogous organization of cis-regulatory elements in which a nuclear matrix attachment region is in close proximity to an enhancer is conserved in the immunoglobulin and T cell receptor loci. In addition, we show that MAR expressed by an individual T cell (4, 5). After V ␤ D ␤ J ␤ rearrangement, a mature transcript is initiated from the V ␤ promoter in a T cell-specific manner (6). To achieve the lineage-, stage-, and allele-specific TCR␤ gene rearrangement and transcription, many cis-acting elements and their associated transacting factors are likely to be involved (4, 5).To date, the TCR␤ gene enhancer (E ␤ ) is the only cis-regulatory element demonstrated to be required for both the lineage-and stage-specific transcription and rearrangement of the TCR␤ gene (7-12). Although the V ␤ promoter is required for lineage-specific TCR␤ transcription, its role in regulating V ␤ gene rearrangement remains unclear (13-17). In addition to V ␤ promoters and E ␤ , there are likely other cis-regulatory elements involved in the control of various aspects of TCR␤ gene rearrangement and transcription. In particular, nuclear matrix attachment regions (MAR) are a class of cis-regulatory elements found in many genetic loci that are distinct from transcriptional promoters and enhancers, and yet are often closely associated with these regulatory elements (18 -20). MARs are typically AT-rich DNA sequences that bind to the nuclear matrix, often contain topoisomerase II cleavage sites, and exhibit a propensity for base unpairing when subjected to superhelical strain (21, 22). They have been proposed to be involved in transcription, DNA recombination, replication, and repair (23). In the immunoglobulin heavy chain (IgH) locus, MARs flank the intronic enhancer E and are in close proximity to V H promoters (22)(23)(24)(25)(26). Reporter gene assays in cell lines and transgenic mice have suggested that these MARs exert both positive and negative effects on IgH gene transcription and promote long range chromatin accessibility (27-31). A highly conserved MAR is also found 200 base pairs (bp) upstream of the intronic immunoglobulin (Ig) enhancer in mouse, human, and rabbit (22,32). Together, the Ig MAR and enhancer promote demethylation, transcription, recombination, and somatic hypermutation of the locus although no specific function has been attributed to the MAR alone (33-36). The presence of MARs at other antigen receptor loci has not been reported.To characteriz...

show abstract

“…It has been reported that RAG-2 is not expressed naturally in mature lymphocytes [4,10]. The abnormal expression maybe implies that Ep needs to associate with an additional flanking region, such as a matrix attachment region, for its correct regulation in vivo [27,28]. Alternatively, Ep may have to interact with another negative regulatory element, such as a silencer, to specifically prevent its activation in mature B cells.…”

mentioning

confidence: 99%

Characterization of the proximal enhancer element and transcriptional regulatory factors for murine recombination activating gene‐2

et al. 2005

View full text Add to dashboard Cite

Recombination-activating gene (RAG)-1 and RAG-2 are essential for V(D)J recombination and are expressed specifically in lymphoid cells. We previously identified two putative enhancer elements, the proximal and distal enhancers, located at -2.6 and -8 kb, respectively, 5 0 upstream of mouse RAG-2, and characterized the distal enhancer element in detail. In this study, to characterize the proximal enhancer in vitro as well as in vivo, we first defined a 170-bp core enhancer element within the proximal enhancer (Ep) and determined its activity in various cells. Ep conferred enhancer activity only in B-lymphoid cell lines, but not in T-or non-lymphoid cell lines. Analysis of the transgenic mice carrying an EGFP reporter gene linked with Ep revealed that Ep activated the transcription of the reporter gene in bone marrow and spleen, but not in thymus or non-lymphoid tissues. Ep was active in both B220 + IgM -and B220 + IgM + subpopulations in the bone marrow and in the B220 + subpopulation in the spleen. Using electrophoretic mobility shift assays and mutational assays, we found that Ikaros and CCAAT/enhancer binding protein cooperatively bind Ep and function as the transcription factors responsible for B cell-specific enhancer activity. These results demonstrate the role of Ep as a cis-regulatory enhancer element for RAG-2-specific expression in B-lymphoid lineages. IntroductionAssembly of Ig and TCR genes by V(D)J recombination is mediated by the products of recombination-activating gene (RAG)-1 and RAG-2 [1, 2]. RAG proteins act together to recognize recombination signal sequences that flank V, D, and J gene segments and introduce the double-stranded DNA breaks between the recombination signal sequences and the gene segments [3]. The expression of RAG-1 and RAG-2 is restricted to lymphoid cells undergoing V(D)J rearrangement [4, 5]. In the absence of either RAG-1 or RAG-2 gene products, the development of mature lymphocytes is completely abrogated and hence results in severe combined immune deficiency in mouse and human [6][7][8]. In human, missense mutations in either RAG-1 or RAG-2 result in the Omenn syndrome, which is characterized by a poor T lymphocyte repertoire [9].There are two waves of RAG-1 and RAG-2 expression in bone marrow B cell precursors. RAG are expressed first in pro-B cell progenitors undergoing Ig heavy-chain gene rearrangement, and the second expression of RAG is seen during Ig j or k light-chain gene rearrangement occurring in pre-B cells [4,10]. In T cell development, RAG areThe first two authors contributed to this work equally. first expressed in pro-T cells when rearrangement of the TCRb chain gene occurs, and secondary expression of RAG occurs when the TCRa chain loci undergo V-J rearrangement to produce mature T cells [11,12]. The transcription of RAG is regulated at different levels. At the chromatin level, Fuller et al. and we reported that a DNase I-hypersensitive (HS) site was identified in the promoter region of mouse and human RAG-1 only in RAG-expressing lymphocytes [13,14]. We a...

show abstract

A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.

Cited by 108 publications

References 56 publications

CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

CDP Is a Repressor of Mouse Mammary Tumor Virus Expression in the Mammary Gland

A Nuclear Matrix Attachment Region Upstream of the T Cell Receptor β Gene Enhancer Binds Cux/CDP and SATB1 and Modulates Enhancer-dependent Reporter Gene Expression but Not Endogenous Gene Expression

Characterization of the proximal enhancer element and transcriptional regulatory factors for murine recombination activating gene‐2

Contact Info

Product

Resources

About