The IgH 3' regulatory region (3'RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3'RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the center of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. Evolution maintained in mammals this unique palindromic arrangement suggesting that it is functionally significant. We report that deconstructing the palindromic IgH 3'RR strongly impacts its function even when enhancers are preserved. CSR and IgH transcription appear poorly dependent from the 3'RR architecture and are more or less preserved provided 3'RR enhancers are present. By contrast, an “architectural effect” significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3'RR does not simply pile up enhancer units but also optimally expose them into a functional architecture of crucial importance. Overall design: RNAseq analysis of B-cell splenocytes with (S=stimulated) or without (R=resting) LPS activation from wt, delta2leftPAL, and deltaIRIS mice.
Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3' regulatory region.
Specimen part, Cell line, Subject
View SamplesWe evaluated by RNA-seq obveral transcripts in B cells (resting and activated for 2 days with LPS) sorted from several KO mice models devoid of portion or all the IgH 3'' Regulatory Region Overall design: One RNA-seq point was realized per condition (resting or stimulated) and per genotype. Each point corresponds to a pool of equivalent number of B cells sorted from 4 animals
Sequential activation and distinct functions for distal and proximal modules within the IgH 3' regulatory region.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
Specimen part, Treatment
View SamplesWe used microarrays to asses gene expression in 3T3 fibroblasts, after knock-down of Brg1 and Brm using stable shRNA interference. Cells were treated with 5ng/ml mouse TNF-alpha to stimulate inducible gene activation.
Role of cell-type specific nucleosome positioning in inducible activation of mammalian promoters.
No sample metadata fields
View SamplesAmong acute myeloid leukemias (AML) with normal karyotype (CN-AML), NPM1 and CEBPA mutations define WHO provisional entities accounting for ~60% of cases, but the remaining ~40% remains poorly characterized. By whole exome-sequencing (WES) of one CN-AML patient lacking mutations in NPM1, CEBPA, FLT3, MLL-PTD and IDH1, we newly identified a clonal somatic mutation in BCOR (BCL6 co-repressor), a gene located in chromosome X. Further analyses showed that BCOR mutations occurred in 11/262 (4.2%) CN-AML cases and represented a substantial fraction (14/82, 17.1%) of CN-AML patients showing the same genetic background as the index patient subjected to WES.
Whole-exome sequencing identifies somatic mutations of BCOR in acute myeloid leukemia with normal karyotype.
Disease
View Samples