Mononuclear Phagocyte Biology &
Epigenetics of Cell Differentiation
Journal Club

Zellbiologisches Literaturseminar für Doktoranden (Vst. Nr. 56265)
Thursday 9:00 am, biweekly
in D53.320 (LIT seminar room) and via Zoom


next date: 01.02.2023
In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis

David Lara-Astiaso, Ainhoa Goñi-Salaverri, Julen Mendieta-Esteban, Nisha Narayan, Cynthia Del Valle, Torsten Gross, George Giotopoulos, Tumas Beinortas, Mar Navarro-Alonso, Laura Pilar Aguado-Alvaro, Jon Zazpe, Francesco Marchese, Natalia Torrea, Isabel A. Calvo, Cecile K. Lopez, Diego Alignani, Aitziber Lopez, Borja Saez, Jake P. Taylor-King, Felipe Prosper, Nikolaus Fortelny & Brian J. P. Huntly

Nature Genetics | volume 55 | pages 1542–1554 (2023)

Cellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of chromatin and transcription factors. By contrast with transcription factors, the roles of chromatin factors in differentiation have not been systematically characterized. Here, we combine bulk ex vivo and single-cell in vivo CRISPR screens to characterize the role of chromatin factor families in hematopoiesis. We uncover marked lineage specificities for 142 chromatin factors, revealing functional diversity among related chromatin factors (i.e. barrier-to-autointegration factor subcomplexes) as well as shared roles for unrelated repressive complexes that restrain excessive myeloid differentiation. Using epigenetic profiling, we identify functional interactions between lineage-determining transcription factors and several chromatin factors that explain their lineage dependencies. Studying chromatin factor functions in leukemia, we show that leukemia cells engage homeostatic chromatin factor functions to block differentiation, generating specific chromatin factor–transcription factor interactions that might be therapeutically targeted. Together, our work elucidates the lineage-determining properties of chromatin factors across normal and malignant hematopoiesis.

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Schedule

01.02.24 AG Rehli
29.02.24 AG Poeck
21.03.24 AG Kreutz
11.04.24 AG Pukrop
25.04.24 AG Rehli
16.05.24 AG Poeck
06.06.24 AG Hansmann
20.06.24 AG Hoffmann
04.07.24 AG Kreutz
18.07.24 AG Rehli

last updated: 25.01.2024


Michael Rehli • Dept. Internal Medicine III • University Hospital
F.-J.-Strauss Allee 11 • 93053 Regensburg • Germany

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