Epigenetic changes on DNA and chromatin are implicated in cell differentiation and organogenesis. For the heart, distinct histone methylation profiles were recently linked to stage-specific gene expression programs during cardiac differentiation in vitro. However, the enzymes catalyzing these modifications and the genes regulated by them remain poorly defined. We therefore decided to identify the epigenetic enzymes that are potentially involved in cardiomyogenesis by analyzing the expression profile of the 85 genes encoding the epigenetic-related proteins in mouse cardiomyocytes (CMs), and then study how they affect gene expression during differentiation and maturation of this cell type. We show here with gene expression screening of epigenetic enzymes that the highly expressed H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) drives a transitional pattern of di-methylation on H3 lysine 79 (H3K79) in CMs at different stages of differentiation in vitro and in vivo. Through a genome-wide chromatin-immunoprecipitation DNA-sequencing approach, we found H3K79me2 enriched at genes expressed during cardiac differentiation. Moreover, knockdown of Dot1L affected the expression of H3K79me2-enriched genes. Our results demonstrate that histone methylation, and in particular DOT1L-mediated H3K79me2 modification, drives cardiomyogenesis through the definition of a specific transcriptional landscape.

DOT1L-mediated H3K79me2 modification critically regulates gene expression during cardiomyocyte differentiation / Cattaneo, P.; Kunderfranco, P.; Greco, C.; Guffanti, A.; Stirparo, G. G.; Rusconi, F.; Rizzi, R.; Di Pasquale, E.; Locatelli, S. L.; Latronico, M. V. G.; Bearzi, C.; Papait, R.; Condorelli, G.. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - 23:4(2016), pp. 555-564. [10.1038/cdd.2014.199]

DOT1L-mediated H3K79me2 modification critically regulates gene expression during cardiomyocyte differentiation

Guffanti A.;Rusconi F.;Rizzi R.;Condorelli G.
2016

Abstract

Epigenetic changes on DNA and chromatin are implicated in cell differentiation and organogenesis. For the heart, distinct histone methylation profiles were recently linked to stage-specific gene expression programs during cardiac differentiation in vitro. However, the enzymes catalyzing these modifications and the genes regulated by them remain poorly defined. We therefore decided to identify the epigenetic enzymes that are potentially involved in cardiomyogenesis by analyzing the expression profile of the 85 genes encoding the epigenetic-related proteins in mouse cardiomyocytes (CMs), and then study how they affect gene expression during differentiation and maturation of this cell type. We show here with gene expression screening of epigenetic enzymes that the highly expressed H3 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) drives a transitional pattern of di-methylation on H3 lysine 79 (H3K79) in CMs at different stages of differentiation in vitro and in vivo. Through a genome-wide chromatin-immunoprecipitation DNA-sequencing approach, we found H3K79me2 enriched at genes expressed during cardiac differentiation. Moreover, knockdown of Dot1L affected the expression of H3K79me2-enriched genes. Our results demonstrate that histone methylation, and in particular DOT1L-mediated H3K79me2 modification, drives cardiomyogenesis through the definition of a specific transcriptional landscape.
2016
epigentic
01 Pubblicazione su rivista::01a Articolo in rivista
DOT1L-mediated H3K79me2 modification critically regulates gene expression during cardiomyocyte differentiation / Cattaneo, P.; Kunderfranco, P.; Greco, C.; Guffanti, A.; Stirparo, G. G.; Rusconi, F.; Rizzi, R.; Di Pasquale, E.; Locatelli, S. L.; Latronico, M. V. G.; Bearzi, C.; Papait, R.; Condorelli, G.. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1350-9047. - 23:4(2016), pp. 555-564. [10.1038/cdd.2014.199]
File allegati a questo prodotto
File Dimensione Formato  
Cattaneo_DOT1L-mediated_2016.pdf

accesso aperto

Note: https://www.nature.com/articles/cdd2014199
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 3.11 MB
Formato Adobe PDF
3.11 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1644881
Citazioni
  • ???jsp.display-item.citation.pmc??? 32
  • Scopus 50
  • ???jsp.display-item.citation.isi??? 43
social impact