Crosstalk between chromatin and Shavenbaby defines transcriptional output along the Drosophila intestinal stem cell lineage
Alexandra Mancheno-Ferris,
Clément Immarigeon,
Alexia Rivero,
David Depierre,
Naomi Schickele,
Olivier Fosseprez,
Nicolas Chanard,
Gabriel Aughey,
Priscilla Lhoumaud,
Julien Anglade,
Tony Southall,
Serge Plaza,
François Payre,
Olivier Cuvier,
Cédric Polesello
Affiliations
Alexandra Mancheno-Ferris
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Control of cell shape remodeling team, CBI, CNRS, UPS, 31062 Toulouse, France
Clément Immarigeon
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Control of cell shape remodeling team, CBI, CNRS, UPS, 31062 Toulouse, France
Alexia Rivero
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Control of cell shape remodeling team, CBI, CNRS, UPS, 31062 Toulouse, France
David Depierre
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Chromatin Dynamics and Cell Proliferation team, CBI, CNRS, UPS, 31062 Toulouse, France
Naomi Schickele
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Chromatin Dynamics and Cell Proliferation team, CBI, CNRS, UPS, 31062 Toulouse, France
Olivier Fosseprez
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Chromatin Dynamics and Cell Proliferation team, CBI, CNRS, UPS, 31062 Toulouse, France
Nicolas Chanard
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Chromatin Dynamics and Cell Proliferation team, CBI, CNRS, UPS, 31062 Toulouse, France
Gabriel Aughey
Imperial College London, Sir Ernst Chain Building, South Kensington Campus, London SW7 2AZ, UK
Priscilla Lhoumaud
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Chromatin Dynamics and Cell Proliferation team, CBI, CNRS, UPS, 31062 Toulouse, France; Institut Jacques Monod, Université Paris Cité/CNRS, 15 rue Hélène Brion, 75205 Paris Cedex 13, France
Julien Anglade
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Chromatin Dynamics and Cell Proliferation team, CBI, CNRS, UPS, 31062 Toulouse, France
Tony Southall
Imperial College London, Sir Ernst Chain Building, South Kensington Campus, London SW7 2AZ, UK
Serge Plaza
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Laboratoire de Recherche en Sciences Végétales, CNRS/UPS/INPT, 31320 Auzeville-Tolosane, France
François Payre
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Control of cell shape remodeling team, CBI, CNRS, UPS, 31062 Toulouse, France
Olivier Cuvier
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Chromatin Dynamics and Cell Proliferation team, CBI, CNRS, UPS, 31062 Toulouse, France; Corresponding author
Cédric Polesello
Molecular, Cellular and Developmental biology department (MCD), Centre de Biologie Integrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France; Control of cell shape remodeling team, CBI, CNRS, UPS, 31062 Toulouse, France; Corresponding author
Summary: The transcription factor Shavenbaby (Svb), the only member of the OvoL family in Drosophila, controls the fate of various epithelial embryonic cells and adult stem cells. Post-translational modification of Svb produces two protein isoforms, Svb-ACT and Svb-REP, which promote adult intestinal stem cell renewal or differentiation, respectively. To define Svb mode of action, we used engineered cell lines and develop an unbiased method to identify Svb target genes across different contexts. Within a given cell type, Svb-ACT and Svb-REP antagonistically regulate the expression of a set of target genes, binding specific enhancers whose accessibility is constrained by chromatin landscape. Reciprocally, Svb-REP can influence local chromatin marks of active enhancers to help repressing target genes. Along the intestinal lineage, the set of Svb target genes progressively changes, together with chromatin accessibility. We propose that Svb-ACT-to-REP transition promotes enterocyte differentiation of intestinal stem cells through direct gene regulation and chromatin remodeling.
