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  ZFP451-mediated SUMOylation of SATB2 drives embryonic stem cell differentiation

Antonio Urrutia, G., Ramachandran, H., Cauchy, P., Boo, K., Ramamoorthy, S., Boller, S., et al. (2021). ZFP451-mediated SUMOylation of SATB2 drives embryonic stem cell differentiation. Genes and Development, 35, 1143-1160. doi:10.1101/gad.345843.120.

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Antonio Urrutia et al. 2021.pdf (Publisher version), 14MB
 
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Antonio Urrutia, Gustavo1, Author
Ramachandran, Haribaskar1, Author
Cauchy, Pierre1, Author
Boo, Kyungjin1, Author
Ramamoorthy, Senthilkumar1, Author
Boller, Sören1, Author              
Dogan, Esen2, Author
Clapes, Thomas1, Author              
Trompouki, Eirini1, Author              
Torres-Padilla, Maria-Elena3, Author
Palvimo, Jorma J3, Author
Pichler, Andrea2, Author              
Grosschedl, Rudolf1, Author              
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              
3External Organizations, ou_persistent22              

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Free keywords: ES cell; LSD1; SATB1; SATB2; SUMO2; ZFP451; differentiation; pluripotency
 Abstract: The establishment of cell fates involves alterations of transcription factor repertoires and repurposing of transcription factors by post-translational modifications. In embryonic stem cells (ESCs), the chromatin organizers SATB2 and SATB1 balance pluripotency and differentiation by activating and repressing pluripotency genes, respectively. Here, we show that conditional Satb2 gene inactivation weakens ESC pluripotency, and we identify SUMO2 modification of SATB2 by the E3 ligase ZFP451 as a potential driver of ESC differentiation. Mutations of two SUMO-acceptor lysines of Satb2 (Satb2K→R) or knockout of Zfp451 impair the ability of ESCs to silence pluripotency genes and activate differentiation-associated genes in response to retinoic acid (RA) treatment. Notably, the forced expression of a SUMO2-SATB2 fusion protein in either Satb2K→R or Zfp451-/- ESCs rescues, in part, their impaired differentiation potential and enhances the down-regulation of Nanog The differentiation defect of Satb2K→R ESCs correlates with altered higher-order chromatin interactions relative to Satb2 wt ESCs. Upon RA treatment of Satb2 wt ESCs, SATB2 interacts with ZFP451 and the LSD1/CoREST complex and gains binding at differentiation genes, which is not observed in RA-treated Satb2K→R cells. Thus, SATB2 SUMOylation may contribute to the rewiring of transcriptional networks and the chromatin interactome of ESCs in the transition of pluripotency to differentiation.

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Language(s): eng - English
 Dates: 2021-07-08
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1101/gad.345843.120
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Title: Genes and Development
Source Genre: Journal
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Publ. Info: Cold Spring Harbor Laboratory Press
Pages: - Volume / Issue: 35 Sequence Number: - Start / End Page: 1143 - 1160 Identifier: ISSN: 0890-9369
CoNE: https://pure.mpg.de/cone/journals/resource/954925557453