Dataset Information

New roles for DNA cytosine modification, eRNA, anchors and super-anchors in developing B cell progenitors

ABSTRACT: B cell fate is orchestrated by a series of well-characterized developmental regulators. Here we found that the onset of B cell development was accompanied by large-scale changes in DNA cytosine modifications associated with promoters, enhancers and anchors. These changes were tightly linked to alterations in transcription factor occupancy and eRNA transcription. We found that the pre-pro-B to the pro-B cell transition was associated with a global exchange of DNA cytosine modifications for polycomb-mediated repression at CpG islands. Hypomethylated regions were found exclusively in the active/permissive compartment of the nucleus and were predominantly associated with regulatory elements or anchors that orchestrate the folding patterns of the genome. We identified super-anchors, characterized by clusters of hypomethylated CTCF-bound elements, which were predominantly located at boundaries that define topological domains (TAD). A particularly prominent hypomethylated super-anchor was positioned down-stream of the immunoglobulin heavy chain (Igh) locus. Analysis of global formaldehyde-cross linking studies indicated that the Igh locus super-anchor interacts with the VH region repertoire across vast genomic distances. We propose that the Igh locus super-anchor sequesters the VH and DHJH regions into a spatial confined geometric environment to promote rapid first-passage times. Collectively, these studies demonstrate how DNA cytosine modifications associated with regulatory and architectural elements affects patterns of gene expression, folding patterns of the genome and antigen receptor assembly in developing B-lineage cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE72670 | GEO | 2015/09/28

SECONDARY ACCESSION(S): PRJNA294623

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Non-coding sense and antisense germline transcription within the immunoglobulin heavy chain locus precedes V(D)J recombination and has been proposed to be associated with Igh locus accessibility, although its precise role remains elusive. However, no global analysis of germline transcription throughout the Igh locus has been done. Therefore, we performed directional RNAseq, demonstrating the locations and extent of both sense and antisense transcription throughout the Igh locus. Surprisingly, the majority of antisense transcripts are localized around two PAIR elements in the distal IghV region. Importantly, long-distance loops measured by 3C are observed between these two active PAIR promoters and Eμ, the start site of Iμ germline transcription, in a lineage- and stage-specific manner, even though this antisense transcription is Eμ-independent. YY1-/- pro-B cells are greatly impaired in distal VH gene rearrangement and Igh locus compaction, and we demonstrate that YY1 deficiency greatly reduces antisense transcription and PAIR-Eμ interactions. ChIP-seq shows high level YY1 binding only at Eμ, but low levels near some antisense promoters. PAIR-Eμ interactions are not disrupted by DRB, which blocks transcription elongation without disrupting transcription factories once they are established, but the looping is reduced after heat shock treatment, which disrupts transcription factories. We propose that transcription-mediated interactions, most likely at transcription factories, initially compact the Igh locus, bringing distal VH genes close to the DJH rearrangement, which is adjacent to Eμ. Therefore, we hypothesize that one key role of non-coding germline transcription is to facilitate locus compaction, allowing distal VH genes to undergo efficient rearrangement. In order to determine the amount and location of sense and antisense non-coding RNA in the Igh locus, we prepared total RNA from CD19+ RAG1-/- pro-B cells. Samples were either pre-enriched in custom Agilent arrays, or directly sequenced. Data from one sample for each condition is included as reflected in the publication.

Dataset Information

New roles for DNA cytosine modification, eRNA, anchors and super-anchors in developing B cell progenitors

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets