Pioneer factors: Emerging rules of engagement for transcription factors on chromatinized DNA.

Pioneering transcription factors (TFs) can drive cell fate changes by binding their DNA motifs in a repressive chromatin environment. Recent structures illustrate emerging rules for nucleosome engagement: TFs distort the nucleosomal DNA to gain access or employ alternative DNA-binding modes with smaller footprints, they preferentially access solvent-exposed motifs near the entry/exit sites, and frequently interact with histones. The extent of TF-histone interactions, in turn, depends on the motif location on the nucleosome, the type of DNA-binding fold, and adjacent domains present.

A direct interaction between CPF and RNA Pol II links RNA 3' end processing to transcription.

Transcription termination by RNA polymerase II (RNA Pol II) is linked to RNA 3' end processing by the cleavage and polyadenylation factor (CPF or CPSF). CPF contains endonuclease, poly(A) polymerase, and protein phosphatase activities, which cleave and polyadenylate pre-mRNAs and dephosphorylate RNA Pol II to control transcription. Exactly how the RNA 3' end processing machinery is coupled to transcription remains unclear.

Organizational Principles of the NuMA-Dynein Interaction Interface and Implications for Mitotic Spindle Functions.

Mitotic progression is orchestrated by the microtubule-based motor dynein, which sustains all mitotic spindle functions. During cell division, cytoplasmic dynein acts with the high-molecular-weight complex dynactin and nuclear mitotic apparatus (NuMA) to organize and position the spindle. Here, we analyze the interaction interface between NuMA and the light intermediate chain (LIC) of eukaryotic dynein.

Hexameric NuMA:LGN structures promote multivalent interactions required for planar epithelial divisions.

Cortical force generators connect epithelial polarity sites with astral microtubules, allowing dynein movement to orient the mitotic spindle as astral microtubules depolymerize. Complexes of the LGN and NuMA proteins, fundamental components of force generators, are recruited to the cortex by Gαi-subunits of heterotrimeric G-proteins. They associate with dynein/dynactin and activate the motor activity pulling on astral microtubules.

Electrophysiological markers of poor versus superior math abilities in healthy individuals.

Interindividual differences in the numerical ability of healthy adults have been previously demonstrated, mainly with tasks involving mental number line or size representation. However, electrophysiological correlates of superior versus poor arithmetic ability (in the healthy population) have been scarcely investigated. We correlated electric potentials with math performance in 13 skilled and 13 poor calculators selected from a sample of 41 graduate students on the basis of their poor or superior math abilities assessed through a timed test.

The APT complex is involved in non-coding RNA transcription and is distinct from CPF.

The 3'-ends of eukaryotic pre-mRNAs are processed in the nucleus by a large multiprotein complex, the cleavage and polyadenylation factor (CPF). CPF cleaves RNA, adds a poly(A) tail and signals transcription termination. CPF harbors four enzymatic activities essential for these processes, but how these are coordinated remains poorly understood.

Error-related negativity in the skilled brain of pianists reveals motor simulation.

Evidences have been provided of a crucial role of multimodal audio-visuomotor processing in subserving the musical ability. In this paper we investigated whether musical audiovisual stimulation might trigger the activation of motor information in the brain of professional pianists, due to the presence of permanent gestures/sound associations. At this aim EEG was recorded in 24 pianists and naive participants engaged in the detection of rare targets while watching hundreds of video clips showing a pair of hands in the act of playing, along with a compatible or incompatible piano soundtrack.

Molecular mechanisms of asymmetric divisions in mammary stem cells.

Stem cells have the remarkable ability to undergo proliferative symmetric divisions and self-renewing asymmetric divisions. Balancing of the two modes of division sustains tissue morphogenesis and homeostasis. Asymmetric divisions of Drosophila neuroblasts (NBs) and sensory organ precursor (SOP) cells served as prototypes to learn what we consider now principles of asymmetric mitoses.

Crystallization and X-ray diffraction of LGN in complex with the actin-binding protein afadin.

Asymmetric stem-cell divisions are fundamental for morphogenesis and tissue homeostasis. They rely on the coordination between cortical polarity and the orientation of the mitotic spindle, which is orchestrated by microtubule pulling motors recruited at the cortex by NuMA-LGN-Gαi complexes. LGN has emerged as a central component of the spindle-orientation pathway that is conserved throughout species.

NuMA Phosphorylation by Aurora-A Orchestrates Spindle Orientation.

Spindle positioning is essential for tissue morphogenesis and homeostasis. The signaling network synchronizing spindle placement with mitotic progression relies on timely recruitment at the cell cortex of NuMA:LGN:Gαi complexes, in which NuMA acts as a receptor for the microtubule motor Dynein. To study the implication of Aurora-A in spindle orientation, we developed protocols for the partial inhibition of its activity.

Concomitant binding of Afadin to LGN and F-actin directs planar spindle orientation.

Polarized epithelia form by oriented cell divisions in which the mitotic spindle aligns parallel to the epithelial plane. To orient the mitotic spindle, cortical cues trigger the recruitment of NuMA-dynein-based motors, which pull on astral microtubules via the protein LGN. We demonstrate that the junctional protein Afadin is required for spindle orientation and correct epithelial morphogenesis of Caco-2 cysts.