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The landscape of global long-range interactions in human erythroid cells mediated by GATA1 and CTCF during differentiation

ABSTRACT: A network of long-range interactions between functional DNA elements regulates gene expression in a precise spatio-temporal pattern during development. We carried out anti-RNA polymerase II and cohesin ChIA-PET and DNase-seq in Mouse Erythroleukemia (MEL) cells to capture genome-wide changes between open chromatin elements in chromatin interaction graphs (CIGs) during DMSO-induced hemoglobin activation. We found that the change of interaction strength in CIGs is positively correlated to expression changes in corresponding genes as measured by RNA-seq. DNaseI footprints and ChIP-seq data indicate that these long-range interactions are controlled through distinct combinations of transcription factors before and after differentiation, with CTCF or cohesin only mediating half of these interactions, with GATA1, PU.1 and/or other transcription factorsYY1 interactions accounting for an additional 40% of detected interactions. Strikingly, while CTCF and GATA1–mediated interactions were enriched in genes involved in erythrocyte differentiation and mitochondrial regulation, PU.1YY1-mediated interactions were enriched for genes involved in RNA processing, cell cycletranslation, and chromatin organizationhistone remodeling. We further found that two-thirds of MEL DNA elements with long-range interactions as well as 35% of their interactions are conserved in human K562 cells and they show similar combinations of factor occupancy in both species. Our study highlights the importance of quantitative analysis of changes in long-range interaction strengths in quantifying changes in gene expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE110361 | GEO | 2020/02/29

REPOSITORIES: GEO

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The landscape of global-long range interactions in mouse and human blood cell lines mediated by Yy1, GATA1, and CTCF during differentiation

Project description:Abstract: A network of interactions between functional DNA elements regulates gene expression in a precise spatio-temporal pattern during development. This regulation is implemented through many-to-many looping interactions of DNA elements mediated by specific transcription factors such as Ctcf, Gata1 and Yy1. We carried out RNA polymerase II ChIA-PET and DNase-seq in Mouse Erythroleukemia (MEL) cells to capture genomewide changes in the resulting chromatin interaction graphs (CIGs) during DMSO-induced hemoglobin activation. We found that the change of interactions in CIGs is positively correlated to the change of a corresponding genes’ expression as measured by RNA-seq. DNase footprints and ChIP-seq data indicate that these long-range interactions are controlled through distinct combinations of transcription factors before and after differentiation, with Ctcf or cohesin only mediating half of these interactions, and Gata1 and/or Yy1 interactions accounting for an additional 40% of detected interactions. Strikingly, while Ctcf and Gata1–mediated interactions were enriched in genes involved in erythrocyte differentiation and mitochondrial regulation, Yy1-mediated interactions were enriched for genes involved in RNA processing, translation, and histone remodeling. We further found that about two-thirds of MEL DNA elements with long-range interactions as well 35% of these interactions are conserved in human K562 cells and show similar combinations of factor occupancy. Taken together, our study identifies that a large set of long-range interactions between active enhancers and promoters involving RNA Pol II are mediated by factors other than cohesin and Ctcf in both human and mouse.

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Transcription Factors Recruit the Cohesin Loader NIPBL to Promote Chromatin Looping and Long-range Gene Regulation

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