1. Stem Cells and Regenerative Medicine
  2. Chromosomes and Gene Expression

MOF-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

  1. Sarina Ravens
  2. Marjorie Fournier
  3. Tao Ye
  4. Matthieu Stierle
  5. Doulaye Dembele
  6. Virginie Chavant
  7. Làszlò Tora  Is a corresponding author
  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, France
https://doi.org/10.7554/eLife.02104
Share this article
Cite this article
  1. Sarina Ravens
  2. Marjorie Fournier
  3. Tao Ye
  4. Matthieu Stierle
  5. Doulaye Dembele
  6. Virginie Chavant
  7. Làszlò Tora
(2014)
MOF-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation
eLife 3:e02104.
https://doi.org/10.7554/eLife.02104
  2. Download BibTeX
  3. Download .RIS

Abstract

The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cells (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation.

Article and author information

Author details

  1. Sarina Ravens

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.

  2. Marjorie Fournier

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.

  3. Tao Ye

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.

  4. Matthieu Stierle

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.

  5. Doulaye Dembele

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.

  6. Virginie Chavant

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.

  7. Làszlò Tora

    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104 - Inserm U 964, Université de Strasbourg, Illkirch, France
    For correspondence
    laszlo@igbmc.fr
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Danny Reinberg, Howard Hughes Medical Institute, New York University School of Medicine, United States

Version history

  1. Received: December 17, 2013
  2. Accepted: June 3, 2014
  3. Accepted Manuscript published: June 4, 2014 (version 1)
  4. Version of Record published: June 17, 2014 (version 2)

Copyright

© 2014, Ravens et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,405
    views
  • 328
    downloads
  • 39
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sarina Ravens
  2. Marjorie Fournier
  3. Tao Ye
  4. Matthieu Stierle
  5. Doulaye Dembele
  6. Virginie Chavant
  7. Làszlò Tora
(2014)
MOF-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation
eLife 3:e02104.
https://doi.org/10.7554/eLife.02104

Share this article

https://doi.org/10.7554/eLife.02104

Categories and tags

Research organism

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    MOF-associated complexes ensure stem cell identity and Xist repression

    Tomasz Chelmicki, Friederike Dündar ... Asifa Akhtar
    Research Article Updated

    Histone acetyl transferases (HATs) play distinct roles in many cellular processes and are frequently misregulated in cancers. Here, we study the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by targeting promoters and TSS-distal enhancers. In contrast to flies, the MSL complex is not exclusively enriched on the X chromosome, yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix, the major repressor of Xist lncRNA. MSL depletion leads to decreased Tsix expression, reduced REX1 recruitment, and consequently, enhanced accumulation of Xist and variable numbers of inactivated X chromosomes during early differentiation. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs.

    1. Stem Cells and Regenerative Medicine

    Hematopoiesis: Counting blood precursors

    Sarah Duchamp de Chastaigne, Catherine M Sawai
    Insight

    A new mathematical model can estimate the number of precursor cells that contribute to regenerating blood cells in mice.

    1. Cell Biology
    2. Stem Cells and Regenerative Medicine

    Differential regulation by CD47 and thrombospondin-1 of extramedullary erythropoiesis in mouse spleen

    Rajdeep Banerjee, Thomas J Meyer ... David D Roberts
    Research Article

    Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells from Cd47−/− mice. Expression of several genes associated with early stages of erythropoiesis was elevated in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen. In contrast, cells expressing markers of committed erythroid progenitors were more abundant in Cd47−/− spleens but significantly depleted in Thbs1−/− spleens. Single-cell transcriptome and flow cytometry analyses indicated that loss of CD47 is associated with accumulation and increased proliferation in spleen of Ter119−CD34+ progenitors and Ter119+CD34− committed erythroid progenitors with elevated mRNA expression of Kit, Ermap, and Tfrc. Induction of committed erythroid precursors is consistent with the known function of CD47 to limit the phagocytic removal of aged erythrocytes. Conversely, loss of thrombospondin-1 delays the turnover of aged red blood cells, which may account for the suppression of committed erythroid precursors in Thbs1−/− spleens relative to basal levels in wild-type mice. In addition to defining a role for CD47 to limit extramedullary erythropoiesis, these studies reveal a thrombospondin-1-dependent basal level of extramedullary erythropoiesis in adult mouse spleen.