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

Show full item record



Permalink

http://hdl.handle.net/10138/236580

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 . https://doi.org/10.1038/s41467-018-04462-8

Title: SETBP1 induces transcription of a network of development genes by acting as an epigenetic hub
Author: 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
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Department of Biochemistry and Developmental Biology
Date: 2018-06-06
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/236580
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.
Subject: ACUTE MYELOID-LEUKEMIA
SCHINZEL-GIEDION SYNDROME
INTEGRATION SITE 1
MYELOMONOCYTIC LEUKEMIA
SECONDARY MUTATIONS
PHF6 MUTATIONS
SELF-RENEWAL
STEM-CELLS
CHIP-SEQ
EXPRESSION
3111 Biomedicine
3122 Cancers
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41467_018_04462_8.pdf 3.458Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record