RT Journal
A1 Belhocine, Mohamed
A1 Simonin, Mathieu
A1 Abad Flores, José David
A1 Cieslak, Agata
A1 Manosalva, Iris
A1 Pradel, Lydie
A1 Smith, Charlotte
A1 Mathieu, Eve-Lyne
A1 Charbonnier, Guillaume
A1 Martens, Joost H.A.
A1 Stunnenberg, Hendrik G.
A1 Maqbool, Muhammad Ahmad
A1 Mikulasova, Aneta
A1 Russell, Lisa J.
A1 Rico, Daniel
A1 Puthier, Denis
A1 Ferrier, Pierre
A1 Asnafi, Vahid
A1 Spicuglia, Salvatore
T1 Dynamics of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes
JF Genome Research 
JO Genome Research 
YR 2022 
FD July 01 
VO 32 
IS 7 
SP 1328 
OP 1342 
DO 10.1101/gr.266924.120 
UL http://genome.cshlp.org/content/32/7/1328.abstract 
AB Broad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain–associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells. Although broad domains preferentially associate with cell identity and tumor suppressor genes in normal thymocytes, they flag key oncogenes in T-ALL samples. Moreover, the expression of broad domain–associated genes, both coding and noncoding, is frequently deregulated in T-ALL. Using two distinct leukemic models, we showed that the ectopic expression of T-ALL oncogenic transcription factor preferentially impacts the expression of broad domain–associated genes in preleukemic cells. Finally, an H3K4me3 demethylase inhibitor differentially targets T-ALL cell lines depending on the extent and number of broad domains. Our results show that the regulation of broad H3K4me3 domains is associated with leukemogenesis, and suggest that the presence of these structures might be used for epigenetic prioritization of cancer-relevant genes, including long noncoding RNAs.