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Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells.
Development 143, 1788-1799 (2016)
Verlagsversion
Postprint
DOI
PMC
The H3K9me3-specific histone methyltransferase Setdb1 impacts on transcriptional regulation by repressing both developmental genes and retrotransposons. How impaired retrotransposon silencing may lead to developmental phenotypes is currently unclear. Here we show that loss of Setdb1 in pro-B cells completely abrogates B cell development. In pro-B cells, Setdb1 is dispensable for silencing of lineage-inappropriate developmental genes. Instead, we detect strong derepression of endogenous Murine Leukemia Virus (MLV) copies. This activation coincides with an unusual change in chromatin structure with only partial loss of H3K9me3 and unchanged DNA methylation, but strongly increased H3K4me3. Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development critically depends on the proper repression of retrotransposon sequences through Setdb1.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
6.059
1.480
12
19
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Heterochromatin ; Mouse ; Retrotransposon ; Setdb1 ; Unfolded Protein Response; Embryonic Stem-cells; Eset Histone Methyltransferase; Fc-gamma-riib; Progenitor Cells; Differentiation; Networks; Genes; Mice; Retroviruses; Transcripts
Sprache
englisch
Veröffentlichungsjahr
2016
HGF-Berichtsjahr
2016
ISSN (print) / ISBN
0950-1991
e-ISSN
1477-9129
Zeitschrift
Development / Company of Biologists
Quellenangaben
Band: 143,
Heft: 10,
Seiten: 1788-1799
Verlag
Company of Biologists
Verlagsort
Cambridge
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Immunology (IMI)
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er)
Immune Response and Infection
PSP-Element(e)
G-501793-001
WOS ID
WOS:000389588300018
Scopus ID
84968779632
PubMed ID
27013243
Erfassungsdatum
2016-04-18