Journal Article

Postmitotic differentiation of human monocytes requires cohesin-structured chromatin

Raithel, Johanna, Ackermann, Ute, Månsson, Robert, Minderjahn, Julia, Fischer, Alexander, Maier, Konstantin, Nuetzel, Margit, Stanewsky, Hanna, Rehli, Michael, Mendes, Karina, Gebhard, Claudia

2022

Overview

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. How chromatin structure and gene accessibility changes during monocyte differentiation is not clearly defined. Here the authors characterize the chromatin changes during macrophage or dendritic cell maturation from monocytes and the dependence of this upon cohesin and CTCF.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/89 / 38/39 / 45 / 45/15 / 49/91 / 631/208/200 / 631/250/2504/133/2505 / 631/250/2504/342 / 631/337/100/101 / Animals / CCCTC-Binding Factor - genetics / Cell culture / Cell Cycle Proteins - metabolism / Cell differentiation / Chromatin / Chromatin - genetics / Chromosomal Proteins, Non-Histone - metabolism / Cohesin / Cohesins / Cohesion / Conformation / Dendritic cells / Depletion / Enhancers / Epigenetics / Gene expression / Genomes / Humanities and Social Sciences / Humans / Macrophages / Mammals - genetics / Monocytes / Monocytes - metabolism / multidisciplinary / Science / Science (multidisciplinary) / siRNA / Transcriptomes