Unknown,Transcriptomics,Genomics,Proteomics

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Global changes in the nuclear positioning of chromatin domains and genomic interactions that orchestrate B cell fate


ABSTRACT: The genome is folded into domains that are located in either transcriptionally inert or permissive compartments. Here we used genome-wide strategies to characterize domains during B cell development. Structured Interaction Matrix Analysis revealed that CTCF occupancy was primarily associated with intra-domain interactions, whereas p300, E2A, Pax5 and PU.1 were involved with intra- and inter-domain interactions that are developmentally regulated. We identified a spectrum of genes that switched nuclear location during early B cell development. In progenitors the transcriptionally inactive Ebf1 locus was sequestered at the nuclear lamina, thereby preserving multipotency, however upon development into the pro-B cell stage Ebf1 and other genes switched compartments to establish de novo intra- and inter-domain interactions that were associated with B lineage specific transcription signatures. Performed Hi-C, GRO-seq, and ChIP-seq to pinpoint the underlying molecular mechanisms that link transcriptional regulation to genomic structure and architecture in lymphocyte development

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Benner 

PROVIDER: E-GEOD-40173 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Global changes in the nuclear positioning of genes and intra- and interdomain genomic interactions that orchestrate B cell fate.

Lin Yin C YC   Benner Christopher C   Mansson Robert R   Heinz Sven S   Miyazaki Kazuko K   Miyazaki Masaki M   Chandra Vivek V   Bossen Claudia C   Glass Christopher K CK   Murre Cornelis C  

Nature immunology 20121014 12


The genome is folded into domains located in compartments that are either transcriptionally inert or transcriptionally permissive. Here we used genome-wide strategies to characterize domains during B cell development. Structured interaction matrix analysis showed that occupancy by the architectural protein CTCF was associated mainly with intradomain interactions, whereas sites bound by the histone acetyltransferase p300 or the transcription factors E2A or PU.1 were associated with intra- and int  ...[more]

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