ERV-derived cryptic enhancers
Our data show that histone methyltransferase SETDB1 is critical for preventing transcription factor (TF) activity on nonphysiological binding sites, in part overlapping with mouse endogenous retrovirus sequences. When SETDB1 is lacking, these cryptic enhancers can become overly active, leading to abnormal expression of nearby genes. This disruption coincides with compromised function of stem…
G4 structures in SVA retrotransposons
G-quadruplexes (G4s) are non-canonical nucleic acid structures that form in guanine-rich regions and play a significant role in regulating the TAF1 gene in X-linked dystonia parkinsonism (XDP). In this condition, a retrotransposon called SVA is inserted into intron 32 of the TAF1 gene, promoting the formation of stable G4s. These G4 structures hinder…
Changed metabolism affects TF activity in T cell lymphoma
PD-1 is a critical tumor suppressor in T cells. Loss of PD-1 in T cell lymphomas results in higher activity of ATP citrate lyase and higer levels of extramitochondrial acetyl-CoA. This allows hyperacetylation of H3K27 in the context of AP-1 transcription factors. Pharmacological inhibition of ATP citrate lyase can counteract aberrant AP-1 activity…
Unveiling EMT Resistance in Metastatic Breast Cancer
This study sheds light on the mechanisms underlying the progression of metastatic breast cancer. Resistance to epithelial-mesenchymal transition (EMT) plays a crucial role in sustaining the clonal propagation of metastatic breast cancer. EPCAM(high) cells from metastatic biopsies have the ability to propagate breast cancer in xenografts. Irreversible EMT leads to restrained tumorigenic potential…
WDR5 as novel druggable target in FSHD
Facioscapulohumeral muscular dystrophy (FSHD) is an inherited progressive neuromuscular disorder. The Gabellini lab could identify WDR5 as critical regulator for aberrant reactivation of DUX4 expression in FSHD, that triggers pathways toxic to skeletal muscle, including inhibition of myogenic differentiation and cell death. WDR5 can be inhibited with a small molecule compound and provides…
new master student
Ata Kan joined the lab as master student to study ERV regulation by the H3.3 turnover pathway.
H3K9me3 not sufficient for ERV silencing
H3K9me3 is not sufficient for silencing endogenous retroviruses if DNA methylation is perturbed. In Dnmt1 ko endoderm cells, IAP elements fully maintain H3K9me3, while trancriptionally active. great collaboration with Heiko Lickert and Heinrich Leonhardt labs, out in Nature Communications
Heterochromatin Nanodomains
How are heterochromatin nanodomains established? Sequence motifs provide nucleation sites, DNA sequence elements, nucleosome interactions and HP1-nucleosome interactions regulate spreading great to be part of this collaboration, out in Nature Communications
GATA2 mutations in leukemia
GATA2 zinc-finger mutations affect hematopoietic differentiation and might help to explain the role of these mutations in chronic myeloid leukemia and erythroleukemia. collaboration paper headed by Philipp Greif, out in Experimental Hematology
HDAC2 in PDAC
HDAC2 has a context-specific role in undifferentiated PDAC and the capacity to disseminate systemically, implicating HDAC2 as targetable protein to prevent metastasis. collaboration headed by Günter Schneider within SFB1321 – out in Cancer Research
The Schotta Lab 