Summary

Epigenetic information is written in chromatin. But how exactly do epigenetic mechanisms operate on the molecular level? How do chromatin alterations contribute to cell fate transitions? How does the environment influence these processes? And how does the metabolic state of a cell impact on its chromatin structure and its epigenetic memory?

These are questions we address in the lab. Studying stem cells and cancer we focus on molecular aspects of epigenetic regulation and on the question whether we can translate this knowledge into diagnostic and therapeutic tools for the management of disease.

Our Research

In our scientific approach we combine biochemical techniques, cell culture and ultrasequencing of enriched chromatin fractions to address mechanistic and functional aspects of epigenetics. As model system for cell differentitiation we are currently using mouse embryonic stem cells, myoblasts and hematopoietic cells. Key findings are validated in vivo. For the study of cancer we combine established cell lines, de novo transformation of primary cultures and patient tissue.

Ongoing projects in the lab fall into four main themes:

  • The study of chromatin regulators affecting embryonic stem cell fate.
  • The link between metabolism and epigenetic regulation.
  • The regulation and molecular function of histone variants.
  • Chromatin as drug target in myeloid dysplastic syndrome and leukemia.

The longest ongoing line of our research focuses on the regulation and function of the histone variant macroH2A. Histones form the proteic core of the nucleosome, which is the modular building block of chromatin structure. MacroH2A is the only histone with a tripartite structure consisting of a N-terminal histone-fold, an intrinsically unstructured linker domain and a C-terminal macro domain. The incorporation of a macroH2A protein into the nucleosome places the macro domain in close proximity to the symmetrical axis and can be considered as the most extensive chromatin modification at the building block level.
From a large set of loss-of-function studies we could conclude that macroH2A is required for the establishment and maintenance of differentiated epigenomes. Although macroH2A is a well-established repressor, we now know that its pro-differetiation function in embryonic stem cells depends at least in part on a poorly understood function in transcriptional activation (Creppe, 2012, MCB). Want to know more? Please have a look at our recent reviews on macroH2A (Creppe, 2012; Posavec, 2013; Cantariño, 2013). In our current work we study the context-dependent function of the macro domain and the regulation of the locus-specific incorporation of macroH2A.
 

To access supplementary material for our publications please click here

Group Members:

Previous Members of Lab:

Catherine Creppe

Melanija Posavec


Awards

  • 2014 Grant from the Spanish Association Contra Cancer (AECC-Junta de Barcelona)
  • 2013 FIRC Fellowship for Stefano Cacciatore, joint Postdoc with Oscar Yanes (URV) and Massimo Loda (Harvard Medical School)
  • 2012 Elected Associate Member of te European Network of Excellence EpiGeneSys
  • 2012 Spanish National Research Grant (MINECO)
  • 2011 Postdoctoral Juan de la Cierva Fellowship to Julien Douet
  • 2010 Ramón and Cajal Award to Marcus Buschbeck
  • 2010 Postdoctoral FEBS Fellowship to Catherine Creppe
  • 2010 Postdoctoral Beatriu Pinos Fellowship to Julien Douet
  • 2010 Spanish PhD Fellowship to Neus Cantariño
  • 2010 Catalan PhD Fellowship to Melanija Posavec
  • 2009 Spanish National Research Grant (MICINN)
  • 2009 Postdoctoral EMBO Fellowship to Catherine Creppe

Contact

mbuschbeck@imppc.org
Office 2-17 Lab 2-15 (second floor)
(+34) 93 554 3065


Chromatin and Cell Fate

Selected Publications

Schnöder TM, Arreba-Tutusaus P, Griehl I, Bullinger L, Buschbeck M, Lane SW, Döhner K, Plass C, Lipka DB, Heidel FH, Fischer T. Epo-induced erythroid maturation is dependent on Plcγ1 signaling. Cell Death Differ. 2015 Jun; 22(6): 974-85

Creppe C, Palau A, Malinverni R, Valero V, Buschbeck M. A Cbx8-Containing Polycomb Complex Facilitates the Transition to Gene Activation during ES Cell Differentiation. PLoS Genet. 2014 Dec; 10(12): e1004851

Palau A, Perucho M, Esteller M, Buschbeck M. First Barcelona Conference on Epigenetics and Cancer. Epigenetics 2014 Mar; 9(3): 468-75

Cong R, Das S, Douet J, Wong J, Buschbeck M, Mongelard F, Bouvet P. macroH2A1 histone variant represses rDNA transcription. Nucleic Acids Res. 2014 Jan; 42(1): 181-92

Posavec M, Timinszky G, Buschbeck M. Macro domains as metabolite sensors on chromatin. Cell. Mol. Life Sci. 2013 May; 70(9): 1509-24

Cantariño N, Douet J, Buschbeck M. MacroH2A - An epigenetic regulator of cancer. Cancer Lett. 2013 Mar;

Creppe C, Janich P, Cantariño N, Noguera M, Valero V, Musulén E, Douet J, Posavec M, Martín-Caballero J, Sumoy L, Di Croce L, Benitah SA, Buschbeck M. MacroH2A1 regulates the balance between self-renewal and differentiation commitment in embryonic and adult stem cells. Mol. Cell. Biol. 2012 Apr; 32(8): 1442-52

Uribesalgo I, Buschbeck M, Gutierrez A, Teichmann S, Demajo S, Kuebler B, Nomdedéu JF, Martín-Caballero J, Roma G, Benitah SA, Di Croce L. E-box-independent regulation of transcription and differentiation by MYC. Nat. Cell Biol. 2011 Dec; 13(12): 1443-9

Buschbeck M, Uribesalgo I, Wibowo I, Rué P, Martin D, Gutierrez A, Morey L, Guigó R, López-Schier H, Di Croce L. The histone variant macroH2A is an epigenetic regulator of key developmental genes. Nat. Struct. Mol. Biol. 2009 Oct; 16(10): 1074-9


See all

Generalitat de Catalunya

Unió Europea

CSIC

Universitat Autònoma de Barcelona

Ajuntament de Badalona

Institut Català de la Salut

Germans Trias i Pujol Hospital

Fundació Institut d'investigació en Ciències de la Salut Germans Trias i Pujol

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