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IGH analysis in pro-B cells with H3K4me3, H3K4me2, H3K9ac, H3K27me3, Pax5 and CTCF [ChIP-chip]

ABSTRACT: VH-DJH recombination of the immunoglobulin heavy-chain (Igh) locus is temporally and spatially controlled during early B-cell development, and yet no regulatory elements other than the VH gene promoters have been identified throughout the entire 2.5-Mb VH gene cluster. Here we discovered novel regulatory sequences that are interspersed in the distal VH gene region. These conserved repeat elements were characterized by the presence of Pax5-dependent active chromatin, the binding of Pax5, E2A, CTCF and Rad21 as well as by Pax5-dependent antisense transcription in pro-B cells. The Pax5-activated intergenic repeat (PAIR) elements were no longer bound by Pax5 in pre-B and B cells consistent with the loss of antisense transcription, whereas E2A and CTCF interacted with PAIR elements throughout early B-cell development. The pro-B-cell-specific and Pax5-dependent activity of the PAIR elements suggests that they are involved in the regulation of distal VH-DJH recombination at the Igh locus. Analysis of chromatin and TF binding in rag2-/- and pax5-/- rag2-/- pro-B cells. Chip-Chip with one experiment for each antibody, 12 samples.

ORGANISM(S): Mus musculus

SUBMITTER: Meinrad Busslinger

PROVIDER: E-GEOD-27074 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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IGH analysis in pro-B cells with H3K4me3, H3K4me2, H3K9ac, H3K27me3, Pax5 and CTCF [ChIP-Seq]

Project description:VH-DJH recombination of the immunoglobulin heavy-chain (Igh) locus is temporally and spatially controlled during early B-cell development, and yet no regulatory elements other than the VH gene promoters have been identified throughout the entire 2.5-Mb VH gene cluster. Here we discovered novel regulatory sequences that are interspersed in the distal VH gene region. These conserved repeat elements were characterized by the presence of Pax5-dependent active chromatin, the binding of Pax5, E2A, CTCF and Rad21 as well as by Pax5-dependent antisense transcription in pro-B cells. The Pax5-activated intergenic repeat (PAIR) elements were no longer bound by Pax5 in pre-B and B cells consistent with the loss of antisense transcription, whereas E2A and CTCF interacted with PAIR elements throughout early B-cell development. The pro-B-cell-specific and Pax5-dependent activity of the PAIR elements suggests that they are involved in the regulation of distal VH-DJH recombination at the Igh locus. Analysis of chromatin and TF binding in rag2-/- and wt pro-B, DP T and Mature B cells. Chip-Seq of CTCF and Rad21. The provided data is in mm8 coordinates.

2011-02-11 | E-GEOD-27214 | biostudies-arrayexpress

IGH analysis in pro-B cells with H3K4me3, H3K4me2 and H3K9ac

Project description:STAT5 and IL-7 signaling are thought to control B-lymphopoiesis by regulating key transcription factor genes and activating VH gene segments at the Igh locus. Using conditional mutagenesis, we demonstrate that transgenic Bcl2 expression rescued the development of Stat5-deleted pro-B cells by compensating for the loss of Mcl-1. Ebf1 and Pax5 expression as well as VH recombination were normal in Bcl2-rescued pro-B cells lacking STAT5 or IL-7Ra. In agreement with this finding, STAT5-expressing pro-B cells contained little or no active chromatin at most VH genes. In contrast, Igk rearrangements were increased in STAT5- or IL-7Ra-deficient pro-B cells, consistent with direct binding of STAT5 to the intronic iEk enhancer in wild-type pro-B cells. Hence, STAT5 and IL-7 signaling control cell survival and suppress premature Igk recombination in early B-lymphopoiesis. comparison of wt vs Rag2-/- pro-B cells

2010-07-28 | E-GEOD-18278 | biostudies-arrayexpress

Chip-chip from pro-B cells with H3K4me3, H3K4me2 and H3K9ac

Project description:The transcription factor Pax5 represses B-lineage-inappropriate genes and activates B-cell-specific genes in B-lymphocytes. Here we have identified 170 novel Pax5-activated genes. Conditional mutagenesis demonstrated that the Pax5-regulated genes require continuous Pax5 activity for normal expression in pro-B and mature B cells. Expression of half of the Pax5-activated genes is either absent or significantly reduced upon Pax5 loss in plasma cells. Direct Pax5 target genes were identified based on their protein synthesis-independent activation by a Pax5-estrogen receptor fusion protein. Chromatin immunoprecipitation (ChIP) of Pax5 together with chromatin profiling by ChIP-on-chip analysis demonstrated that Pax5 directly activates the chromatin at promoters or putative enhancers of Pax5 target genes. The novel Pax5-activated genes code for key regulatory and structural proteins involved in B cell signaling, adhesion, migration, antigen presentation and germinal center B cell formation, thus revealing a complex regulatory network, which is activated by Pax5 to control B cell development and function. Keywords: Chip-chip, cell type comparison comparison of Pax5-/-Rag2-/- vs Rag2-/- pro-B cells

2010-05-20 | E-GEOD-15145 | biostudies-arrayexpress

Chip-chip from pro-B cells with H3K4me3, H3K4me2 and H3K9ac

2007-08-23 | E-GEOD-8472 | biostudies-arrayexpress

The transcription factor Pax5 regulates its target genes by recruiting chromatin-modifying proteins in committed B cells

Project description:Pax5 is a critical regulator of B cell commitment. Here we identified direct Pax5 target genes by streptavidin-mediated ChIP-chip analysis of pro-B cells expressing in vivo biotinylated Pax5. By binding to promoters and enhancers, Pax5 directly regulates the expression of multiple transcription factor, cell surface receptor and signal transducer genes. One of the newly identified enhancers was shown by transgenic analysis to confer Pax5-dependent B-cell-specific activity to the Nedd9 gene controlling B cell trafficking. Profiling of histone modifications in Pax5-deficient and committed wild-type pro-B cells demonstrated that Pax5 induces active chromatin at activated target genes, while eliminating active chromatin at repressed genes in committed pro-B cells. Pax5 rapidly induces these chromatin and transcription changes by recruiting chromatin-remodeling, histone-modifying and basal transcription factor complexes to its target genes. These data provide novel insight into the regulatory network and epigenetic regulation, by which Pax5 controls B cell commitment. Analysis of chromatin and TF binding in rag2-/- and pax5-/- rag2-/- pro-B cells. Chip-Chip with 1-3 experiments for each antibody and celltype combination.

2012-03-29 | E-GEOD-28373 | biostudies-arrayexpress

IGH analysis in pro-B cells with H3K4me3, H3K4me2, H3K9ac, H3K27me3, Pax5 and CTCF [ChIP-Seq]

2011-02-11 | GSE27214 | GEO

IGH analysis in pro-B cells with H3K4me3, H3K4me2, H3K9ac, H3K27me3, Pax5 and CTCF [ChIP-chip]

2011-02-11 | GSE27074 | GEO

Flexible chromatin loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

Project description:The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH- rearranged gene segment in the proximal Igh domain. By high-resolution mapping of long-range interactions, we now demonstrate that an array of local interaction domains establishes the three- dimensional structure of the extended Igh locus in lymphoid progenitors and thymocytes. In pro- B cells, these local domains engage in long-range interactions across the entire Igh locus, which depend on the transcription factors Pax5, YY1 and CTCF. The large VH gene cluster thereby undergoes flexible long-range interactions with the more rigidly structured 3M-bM-^@M-^Y proximal domain, which ensures that all VH genes can participate with similar probability in VH-DJH recombination to generate a diverse antibody repertoire. Notably, these long-range interactions appear to be an intrinsic feature of the VH gene cluster, as they are still generated upon mutation of the EM-NM-< enhancer, IGCR1 insulator or 3M-bM-^@M-^Y regulatory region present in the 3M-bM-^@M-^Y proximal Igh domain. 4C sequencing from mutliple celltypes with multiple viewpoints; uneven number of replicates ChIP-Seq

2013-09-30 | E-GEOD-43008 | biostudies-arrayexpress

Flexible chromatin loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

Project description:The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH- rearranged gene segment in the proximal Igh domain. By high-resolution mapping of long-range interactions, we now demonstrate that an array of local interaction domains establishes the three- dimensional structure of the extended Igh locus in lymphoid progenitors and thymocytes. In pro- B cells, these local domains engage in long-range interactions across the entire Igh locus, which depend on the transcription factors Pax5, YY1 and CTCF. The large VH gene cluster thereby undergoes flexible long-range interactions with the more rigidly structured 3’ proximal domain, which ensures that all VH genes can participate with similar probability in VH-DJH recombination to generate a diverse antibody repertoire. Notably, these long-range interactions appear to be an intrinsic feature of the VH gene cluster, as they are still generated upon mutation of the Eμ enhancer, IGCR1 insulator or 3’ regulatory region present in the 3’ proximal Igh domain.

2013-09-30 | GSE43008 | GEO

Loop Extrusion Mediates Physiological Locus Contraction for V(D)J Recombination (3C-HTGTS)

Project description:Immunoglobulin heavy chain locus (Igh) VH, D, and JH gene segments are developmentally assembled into V(D)J exons. RAG endonuclease initiates V(D)J recombination by binding a JH-recombination signal sequence (RSS) within a chromatin-based recombination center (RC) and then, in an orientation-dependent process, scans upstream D-containing chromatin presented by cohesin-mediated loop extrusion for convergent D-RSSs to initiate DJH-RC formation. In primary pro-B cells, 100s of upstream VH-associated RSSs, embedded in convergent orientation to the DJH-RC-RSS, gain proximity to the DJH-RC for VH-to-DJH joining via a mechanistically-undefined VH-locus contraction process. Here, we report that a 2.4 mega-base VH locus inversion in primary pro-B cells nearly abrogates rearrangements of normally convergent VH-RSSs and cryptic RSSs, even though locus contraction per se is maintained. Moreover, this inversion activated rearrangement of both cryptic VH-locus RSSs normally in the opposite orientation and, unexpectedly, of normally-oriented cryptic RSSs within multiple, sequential upstream convergent-CBE domains. Primary pro-B cells had significantly reduced transcription of Wapl, a cohesin-unloading factor, versus levels in v-Abl pro-B lines that lack marked locus contraction or distal VH rearrangements. Correspondingly, Wapl depletion in v-Abl lines activated VH-locus contraction and orientation-specific RAG-scanning across the VH-locus. Our findings indicate that locus contraction and physiological VH-to-DJH joining both are regulated via circumvention of CBE scanning impediments.

2020-11-08 | GSE151909 | GEO

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