The genetic elements required to tune gene expression are partitioned in active and repressive nuclear condensates. Chromatin compartments include transcriptional clusters whose dynamic establishment and functioning depends on multivalent interactions occurring among transcription factors, cofactors and basal transcriptional machinery. However, how chromatin players contribute to the assembly of transcriptional condensates is poorly understood. By interrogating the effect of KMT2D (also known as MLL4 ) haploinsufficiency in Kabuki Syndrome, we found that MLL4 contributes to the assembly of transcriptional condensates through liquid-liquid phase separation. MLL4 loss-of-function (LoF) impaired Polycomb-dependent chromatin compartmentalization, altering nuclear architecture. By releasing the nuclear mechanical stress through the inhibition of the mechano-sensor ATR, we re-established the mechano-signaling of mesenchymal stem cells (MSCs) and their commitment towards chondrocytes both in vitro and in vivo. This study supports the notion that in Kabuki Syndrome the haploinsufficiency of MLL4 causes an altered functional partitioning of chromatin, which determines the architecture and mechanical properties of the nucleus.

We report a fully guided-wave source of polarisation entangled photons based on a periodically poled lithium niobate waveguide mounted in a Sagnac interferometer. We demonstrate the source's quality by converting polarisation entanglement to postselection-free energy-time entanglement for which we obtain a near-optimal S-parameter of 2.75 ± 0.02, i.e. a violation of the Bell inequality by more than 35 standard deviations. The exclusive use of guided-wave components makes our source compact and stable which is a prerequisite for increasingly complex quantum applications. Additionally, our source offers a great versatility in terms of photon pair emission spectrum and generated quantum state, making it suitable for a broad range of quantum applications such as cryptography and metrology. In this sense, we show how to use our source for chromatic dispersion measurements in optical fibres which opens new avenues in the field of quantum metrology.

Beyond the use of genuine monolithic integrated optical platforms, we report here a hybrid strategy enabling on-chip generation of configurable heralded two-photon states. More specifically, we combine two different fabrication techniques, i.e., non-linear waveguides on lithium niobate for efficient photon-pair generation and femtosecond-laser-direct-written waveguides on glass for photon manipulation. Through real-time device manipulation capabilities, a variety of path-coded heralded two-photon states can be produced, ranging from product to entangled states. Those states are engineered with high levels of purity, assessed by fidelities of 99.5 ± 8% and 95.0 ± 8%, respectively, obtained via quantum interferometric measurements. Our strategy therefore stands as a milestone for further exploiting entanglement-based protocols, relying on engineered quantum states, and enabled by scalable and compatible photonic circuits.