MSL2 ensures biallelic gene expression in mammals.

In diploid organisms, biallelic gene expression enables the production of adequate levels of mRNA. This is essential for haploinsufficient genes, which require biallelic expression for optimal function to prevent the onset of developmental disorders. Whether and how a biallelic or monoallelic state is determined in a cell-type-specific manner at individual loci remains unclear.

Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus nonciliated cells.

Members of the NSL histone acetyltransferase complex are involved in multiorgan developmental syndromes. While the NSL complex is known for its importance in early development, its role in fully differentiated cells remains enigmatic. Using a kidney-specific model, we discovered that deletion of NSL complex members KANSL2 or KANSL3 in postmitotic podocytes led to catastrophic kidney dysfunction.

Satellite repeat transcripts modulate heterochromatin condensates and safeguard chromosome stability in mouse embryonic stem cells.

Heterochromatin maintains genome integrity and function, and is organised into distinct nuclear domains. Some of these domains are proposed to form by phase separation through the accumulation of HP1ɑ. Mouse heterochromatin contains noncoding major satellite repeats (MSR), which are highly transcribed in mouse embryonic stem cells (ESCs).

Two genomes, one cell: Mitochondrial-nuclear coordination via epigenetic pathways.

Background: Virtually all eukaryotic cells contain spatially distinct genomes, a single nuclear genome that harbours the vast majority of genes and much smaller genomes found in mitochondria present at thousands of copies per cell. To generate a coordinated gene response to various environmental cues, the genomes must communicate with each another. Much of this bi-directional crosstalk relies on epigenetic processes, including DNA, RNA, and histone modification pathways.

Citrullination of HP1γ chromodomain affects association with chromatin.

Background: Stem cell differentiation involves major chromatin reorganisation, heterochromatin formation and genomic relocalisation of structural proteins, including heterochromatin protein 1 gamma (HP1γ). As the principal reader of the repressive histone marks H3K9me2/3, HP1 plays a key role in numerous processes including heterochromatin formation and maintenance.

Results: We find that HP1γ is citrullinated in mouse embryonic stem cells (mESCs) and this diminishes when cells differentiate, indicating that it is a dynamically regulated post-translational modification during stem cell differentiation.

Functional interdependence of BRD4 and DOT1L in MLL leukemia.

Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes.

Induction of the proapoptotic tumor suppressor gene Cell Adhesion Molecule 1 by chemotherapeutic agents is repressed in therapy resistant acute myeloid leukemia.

Even though a large proportion of patients with acute myeloid leukemia (AML) achieve a complete remission upon initial therapy, the majority of them eventually relapse with resistant disease. Overexpression of the gene coding for the transcription factor Ecotropic Virus Integration site 1 (EVI1) is associated with rapid disease recurrence and shortened survival. We therefore sought to identify EVI1 target genes that may play a role in chemotherapy resistance using a previously established in vitro model system for EVI1 positive myeloid malignancies.