Postmitotic differentiation of human monocytes requires cohesin-structured chromatin

Julia Minderjahn, Alexander Fischer, Konstantin Maier, Karina Mendes, Margit Nuetzel, Johanna Raithel, Hanna Stanewsky, Ute Ackermann, Robert Månsson, Claudia Gebhard and Michael Rehli ()
Additional contact information
Julia Minderjahn: University Hospital Regensburg
Alexander Fischer: University Hospital Regensburg
Konstantin Maier: University Hospital Regensburg
Karina Mendes: University Hospital Regensburg
Margit Nuetzel: University Hospital Regensburg
Johanna Raithel: c/o University Hospital Regensburg
Hanna Stanewsky: University Hospital Regensburg
Ute Ackermann: University Hospital Regensburg
Robert Månsson: Karolinska Institutet
Claudia Gebhard: c/o University Hospital Regensburg
Michael Rehli: University Hospital Regensburg

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Cohesin is a major structural component of mammalian genomes and is required to maintain loop structures. While acute depletion in short-term culture models suggests a limited importance of cohesin for steady-state transcriptional circuits, long-term studies are hampered by essential functions of cohesin during replication. Here, we study genome architecture in a postmitotic differentiation setting, the differentiation of human blood monocytes (MO). We profile and compare epigenetic, transcriptome and 3D conformation landscapes during MO differentiation (either into dendritic cells or macrophages) across the genome and detect numerous architectural changes, ranging from higher level compartments down to chromatin loops. Changes in loop structures correlate with cohesin-binding, as well as epigenetic and transcriptional changes during differentiation. Functional studies show that the siRNA-mediated depletion of cohesin (and to a lesser extent also CTCF) markedly disturbs loop structures and dysregulates genes and enhancers that are primarily regulated during normal MO differentiation. In addition, gene activation programs in cohesin-depleted MO-derived macrophages are disturbed. Our findings implicate an essential function of cohesin in controlling long-term, differentiation- and activation-associated gene expression programs.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-31892-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31892-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-31892-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().