SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub

Show simple item record Piazza, Rocco Magistroni, Vera Redaelli, Sara Mauri, Mario Massimino, Luca Sessa, Alessandro Peronaci, Marco Lalowski, Maciej Soliymani, Rabah Mezzatesta, Caterina Pirola, Alessandra Banfi, Federica Rubio, Alicia Rea, Delphine Stagno, Fabio Usala, Emilio Martino, Bruno Campiotti, Leonardo Merli, Michele Passamonti, Francesco Onida, Francesco Morotti, Alessandro Pavesi, Francesca Bregni, Marco Broccoli, Vania Baumann, Marc Gambacorti-Passerini, Carlo 2018-06-21T07:56:01Z 2018-06-21T07:56:01Z 2018-06-06
dc.identifier.citation Piazza , R , Magistroni , V , Redaelli , S , Mauri , M , Massimino , L , Sessa , A , Peronaci , M , Lalowski , M , Soliymani , R , Mezzatesta , C , Pirola , A , Banfi , F , Rubio , A , Rea , D , Stagno , F , Usala , E , Martino , B , Campiotti , L , Merli , M , Passamonti , F , Onida , F , Morotti , A , Pavesi , F , Bregni , M , Broccoli , V , Baumann , M & Gambacorti-Passerini , C 2018 , ' SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub ' , Nature Communications , vol. 9 , 2192 .
dc.identifier.other PURE: 107996339
dc.identifier.other PURE UUID: 407cb214-aced-4916-b50f-49190e13e856
dc.identifier.other WOS: 000434258200004
dc.identifier.other Scopus: 85048287225
dc.identifier.other ORCID: /0000-0002-3683-4096/work/77087471
dc.description.abstract SETBP1 variants occur as somatic mutations in several hematological malignancies such as atypical chronic myeloid leukemia and as de novo germline mutations in the Schinzel-Giedion syndrome. Here we show that SETBP1 binds to gDNA in AT-rich promoter regions, causing activation of gene expression through recruitment of a HCF1/KMT2A/PHF8 epigenetic complex. Deletion of two AT-hooks abrogates the binding of SETBP1 to gDNA and impairs target gene upregulation. Genes controlled by SETBP1 such as MECOM are significantly upregulated in leukemias containing SETBP1 mutations. Gene ontology analysis of deregulated SETBP1 target genes indicates that they are also key controllers of visceral organ development and brain morphogenesis. In line with these findings, in utero brain electroporation of mutated SETBP1 causes impairment of mouse neurogenesis with a profound delay in neuronal migration. In summary, this work unveils a SETBP1 function that directly affects gene transcription and clarifies the mechanism operating in myeloid malignancies and in the Schinzel- Giedion syndrome caused by SETBP1 mutations. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject PHF6 MUTATIONS
dc.subject SELF-RENEWAL
dc.subject STEM-CELLS
dc.subject CHIP-SEQ
dc.subject EXPRESSION
dc.subject 3111 Biomedicine
dc.subject 3122 Cancers
dc.title SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub en
dc.type Article
dc.contributor.organization Medicum
dc.contributor.organization Department of Biochemistry and Developmental Biology
dc.contributor.organization University of Helsinki
dc.contributor.organization Marc Baumann / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.issn 2041-1723
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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