Bromodomains have emerged as attractive candidates for the development of inhibitors targeting gene transcription. Inhibitors of the bromo and extraterminal (BET) family recently showed promising activity in diverse disease models. However, the pleiotropic nature of BET proteins regulating tissue-specific transcription has raised safety concerns and suggested that attempts should be made for do...

AID mis-targeting is poorly understood but contributes significantly to B cell genome instability. Two new papers in Cell reveal that AID mistargeting occurs primarily in gene bodies within a nuclear microenvironment characterized by high levels of transcriptional activity, interconnected transcriptional regulatory elements, and overlapping sense and antisense (convergent) transcription.

Histone H3 phosphorylation is a critical step that couples signal transduction pathways to gene regulation. To specifically assess the transcriptional regulatory functions of H3 phosphorylation, we developed an in vivo targeting approach and found that the H3 kinase MSK1 is a direct and potent transcriptional activator. Targeting of this H3 kinase to the endogenous c-fos promoter is sufficient ...

Abstract In a previous in silico study, we identified an essential outer membrane (OM) protein (LptD) as attractive target for development of novel antibiotics. Here, characterised the effects LptD depletion on Escherichia coli physiology and morphology. An E. CRISPR interference (CRISPRi) strain was constructed to allow control lptD expression. Induction CRISPRi system led ∼440-fold reduction ...

The two-step transcriptional activation (TSTA) mechanism in gene therapy amplifies cell type-specific promoter activity, allowing for increased levels of gene expression in target tissues. In this system, the specific promoter drives expression of a strong transcriptional activator that binds to DNA target sequences located upstream from a second promoter controlling the expression of the thera...

Estrogen-related receptor alpha (ERR1) is an orphan nuclear receptor that can bind transcriptional co-activators constitutively. ERR1 expression correlates with poor patient outcomes in breast cancer, heightening interest in this nuclear receptor as a therapeutic target. Because ERR1 has no known regulatory ligand, a major challenge in targeting its activity is to find cellular or synthetic mod...

Over the last years, discovery of various natural and development a row engineered CRISPR/Cas nucleases have made almost every site plant genomes accessible for induction specific changes. Newly developed tools open up wide range possibilities genetic variability, from changing single bp to Mbps, thus fine-tune performance. Whereas early approaches focused on targeted mutagenesis, recently enab...

Abstract Endemic fluorosis is caused by the intake of high environmental fluoride levels, which causes dental and skeletal fluorosis. Osteoblast proliferation activation closely related to tightly regulated cell cycle. Several biological processes, including bone metabolism osteoblast activation, are a type non-coding RNA called microRNAs (miRNAs). However, understanding miRNA functions in limi...

Histone lysine acylation is a major class of histone post-translational modifications involved in essential biological activities, such as transcriptional regulation, DNA-damage repair, and cell-cycle progression. Abnormal strongly associated with various diseases, cancer. Thus, acetyltransferases (HATs), the “writers” that catalyze acylation, are promising targets for cancer treatment. Rapid d...