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Cell death & disease
04 27, 2020;11 (4): 287.

The H2B ubiquitin-protein ligase RNF40 is required for somatic cell reprogramming.

Wanhua Xie, Michaela Miehe, Sandra Laufer, Steven A Johnsen
Author Information
  1. Wanhua Xie: The Precise Medicine Center, Shenyang Medical College, Shenyang, China. wanhuaxie@icloud.com.
  2. Michaela Miehe: Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  3. Sandra Laufer: Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  4. Steven A Johnsen: Gene Regulatory Mechanisms and Molecular Epigenetics Lab, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. johnsen.steven@mayo.edu. ORCID
PMID: 32341358 DOI: 10.1038/s41419-020-2482-4

Abstract

Direct reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) requires a resetting of the epigenome in order to facilitate a cell fate transition. Previous studies have shown that epigenetic modifying enzymes play a central role in controlling induced pluripotency and the generation of iPSC. Here we show that RNF40, a histone H2B lysine 120 E3 ubiquitin-protein ligase, is specifically required for early reprogramming during induced pluripotency. Loss of RNF40-mediated H2B monoubiquitination (H2Bub1) impaired early gene activation in reprogramming. We further show that RNF40 contributes to tissue-specific gene suppression via indirect effects by controlling the expression of the polycomb repressive complex-2 histone methyltransferase component EZH2, as well as through more direct effects by promoting the resolution of H3K4me3/H3K27me3 bivalency on H2Bub1-occupied pluripotency genes. Thus, we identify RNF40 as a central epigenetic mediator of cell state transition with distinct functions in resetting somatic cell state to pluripotency.

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MeSH Term

Cell Differentiation
Cellular Reprogramming
Humans
Induced Pluripotent Stem Cells
Protein Processing, Post-Translational
Ubiquitin-Protein Ligases

Chemicals

RNF40 protein, human
Ubiquitin-Protein Ligases
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 10

Word Cloud

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