A family of chromatin remodeling factors related to Williams syndrome transcription factor

Bochar, Daniel A.; Savard, Julie; Wang, Weidong; LaFleur, David W.; Moore, Paul A.; Côté, Jacques; Shiekhattar, Ramin

doi:10.1073/pnas.97.3.1038

Cited by 142 publications

(116 citation statements)

References 47 publications

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“…Thus, the RAG2 C terminus might directly facilitate changes in chromatin structure or, more likely, facilitate assembly of the RAG1͞2 complex on RSSs wrapped in chromatin. The association of other PHD-containing proteins with chromatin remodeling and modification (21)(22)(23)(24) is consistent with such a role for RAG2 in influencing the accessibility of antigenreceptor loci. In this context, the PHD motif of RAG2 might serve a unique, undefined function in promoting accessibility of V H and V␤ segments.…”

Section: Discussionsupporting

confidence: 50%

“…Consistent with this notion, studies of Abelson murine leukemia virus-transformed pre-B cells have suggested that the noncore regions of RAG1 are important for IgH locus D H -to-J H rearrangement (17), whereas the C terminus of RAG2 is more important for V H -to-DJ H rearrangement than for D H -to-J H rearrangement (18). The C terminus of RAG2 is predicted to fold into a plant homeodomain (PHD) (19,20), a motif found in a number of chromatin-associated proteins including some that have chromatin-modifying activities (21)(22)(23)(24).…”

Section: Uring B and T Cell Development The Ig And T Cell Receptormentioning

confidence: 99%

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Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice

Akamatsu

Monroe

Dudley

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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During lymphocyte development, V(D)J recombination is highly regulated in the contexts of lineage specificity, developmental-stage specificity, and allelic exclusion (4, 5). In addition, developing lymphocytes use strategies that require productive V(D)J rearrangements for continued developmental progression (4, 5). For example, Ig heavy chain (IgH) variable-region genes are assembled in progenitor (pro) B cells via an ordered process in which D H -to-J H rearrangement occurs on both alleles before V H -to-DJ H rearrangement. Productive V H -to-DJ H rearrangements produce cell-surface expression of IgH chains that signal expansion and differentiation of pro-B cells to the pre-B cell stage. This expression of IgH chains also signals the cessation of further V H -to-DJ H rearrangement via feedback regulation. Pro-B cells that first assemble nonproductive V H -to-DJ H rearrangements proceed to rearrange their second allele.Both RAG1 and RAG2 are required for V(D)J recombination, because RAG1-or RAG2-deficient mice exhibit a complete block in lymphocyte development at the progenitor stage (6, 7). In addition, RAG1 and RAG2 together are sufficient to initiate V(D)J recombination in vitro (8). Nearly all in vitro studies of RAG function have used the minimal regions of RAG1 (amino acids 384-1,008 of 1,040) and RAG2 (amino acids 1-383 of 527) required for activity, because full-length RAG1 and RAG2 are largely insoluble. However, the activities of these mutant ''core'' proteins differ from those of the full-length RAGs when assayed with extrachromosomal substrates in transfected cells. In this context, the mutant core RAG proteins support V(D)J recombination with reduced efficiency and with different levels and types of recombination products (9-15).Although not required for the biochemistry of V(D)J recombination, the noncore regions of RAG1 and RAG2 are conserved throughout evolution. For example, sequence conservation across the entire RAG2 protein from pufferfish to humans is Ϸ60%, with conservation of the noncore C-terminal region slightly higher than the core domain (16). Therefore, the noncore regions of RAG1 and RAG2 may serve important accessory and͞or regulatory functions in chromosomal V(D)J recombination. Consistent with this notion, studies of Abelson murine leukemia virus-transformed pre-B cells have suggested that the noncore regions of RAG1 are important for IgH locus D H -to-J H rearrangement (17), whereas the C terminus of RAG2 is more important for V H -to-DJ H rearrangement than for D H -to-J H rearrangement (18). The C terminus of RAG2 is predicted to fold into a plant homeodomain (PHD) (19,20), a motif found in a number of chromatin-associated proteins including some that have chromatin-modifying activities (21-24).To investigate potential in vivo function of the RAG2 noncore region in chromosomal V(D)J recombination and normal lymphocyte development, we have generated and characterized mice containing specific replacement of the full-length endogenous RAG2 gene with a gene encoding the mouse core...

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Section: Discussionsupporting

confidence: 50%

Section: Uring B and T Cell Development The Ig And T Cell Receptormentioning

confidence: 99%

Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice

Akamatsu

Monroe

Dudley

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…The Drosophila ISWI protein is a common subunit of the NURF, CHRAC and ACF complexes. In vertebrates, members of the ISWI subfamily are the ATPase subunits of the RSF complex, (23) hACF/WCRF complex, (29,45) xACF, (46) WICH complex, (47) hCHRAC (48) and NoRC. (49) In addition, ISW1 and ISW2 are the catalytic subunits of chromatin-remodeling complexes in yeast.…”

Section: Activities Of Chromatin-remodeling Factorsmentioning

confidence: 99%

Chromatin remodeling by ATP‐dependent molecular machines

2003

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SummaryThe eukaryotic genome is packaged into a periodic nucleoprotein structure termed chromatin. The repeating unit of chromatin, the nucleosome, consists of DNA that is wound nearly two times around an octamer of histone proteins. To facilitate DNA-directed processes in chromatin, it is often necessary to rearrange or to mobilize the nucleosomes. This remodeling of the nucleosomes is achieved by the action of chromatin-remodeling complexes, which are a family of ATP-dependent molecular machines. Chromatin-remodeling factors share a related ATPase subunit and participate in transcriptional regulation, DNA repair, homologous recombination and chromatin assembly. In this review, we provide an overview of chromatin-remodeling enzymes and discuss two possible mechanisms by which these factors might act to reorganize nucleosome structure.

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“…Acf-1 is highly homologous to the human protein WSTF (William Syndrome Transcription factor 1), which contains PHD ®ngers and a bromodomain. One of the human homologues of ISWI, hSNF 2 h, has been shown to be a part of a remodelling complex containing WSTF (Bochar et al, 2000). ACF and hSNF 2 h/WSTF represent a class of complexes involved both in chromatin maturation and chromatin remodelling.…”

Section: Chromatin Spacing and Assembly Complexesmentioning

confidence: 99%

Chromatin remodelling and DNA replication: from nucleosomes to loop domains

2001

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Organization of DNA into chromatin is likely to participate in the control of the timing and selection of DNA replication origins. Reorganization of the chromatin is carried out by chromatin remodelling machines, which may a ect the choice of replication origins and e ciency of replication. Replication itself causes a profound rearrangement in the chromatin structure, from nucleosomes to DNA loop domains, allowing to retain or switch an epigenetic state. The present review considers the e ects of chromatin remodelling on replication and vice versa. Oncogene (2001) 20, 3086 ± 3093.

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A family of chromatin remodeling factors related to Williams syndrome transcription factor

Cited by 142 publications

References 47 publications

Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice

Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice

Chromatin remodeling by ATP‐dependent molecular machines

Chromatin remodelling and DNA replication: from nucleosomes to loop domains

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