Phase Separation: Direct and Indirect Driving Force for High-Order Chromatin Organization.

The multi-level spatial chromatin organization in the nucleus is closely related to chromatin activity. The mechanism of chromatin organization and remodeling attract much attention. Phase separation describes the biomolecular condensation which is the basis for membraneless compartments in cells. Recent research shows that phase separation is a key aspect to drive high-order chromatin structure and remodeling. In addition, chromatin functional compartmentalization in the nucleus which is formed by phase separation also plays an important role in overall chromatin structure. In this review, we summarized the latest work about the role of phase separation in spatial chromatin organization, focusing on direct and indirect effects of phase separation on 3D chromatin organization and its impact on transcription regulation.

Functional partitioning of transcriptional regulators by patterned charge blocks.

Components of transcriptional machinery are selectively partitioned into specific condensates, often mediated by protein disorder, yet we know little about how this specificity is achieved. Here, we show that condensates composed of the intrinsically disordered region (IDR) of MED1 selectively partition RNA polymerase II together with its positive allosteric regulators while excluding negative regulators. This selective compartmentalization is sufficient to activate transcription and is required for gene activation during a cell-state transition. The IDRs of partitioned proteins are necessary and sufficient for selective compartmentalization and require alternating blocks of charged amino acids. Disrupting this charge pattern prevents partitioning, whereas adding the pattern to proteins promotes partitioning with functional consequences for gene activation. IDRs with similar patterned charge blocks show similar partitioning and function. These findings demonstrate that disorder-mediated interactions can selectively compartmentalize specific functionally related proteins from a complex mixture of biomolecules, leading to regulation of a biochemical pathway.

Comparison of the electromyographic activity of different zones of the abductor digiti minimi manus muscle in search of a functional compartmentalisation / Comparación de la actividad electromiográfica de diferentes zonas del músculo abductor digiti minimi manus en busca de una compartimentación funcional

SUMMARY: There is evidence demonstrating the presence of functional compartmentalisation (FC) in some skeletal muscles. This means that the motor units (MU), grouped in certain areas of the muscle, show different levels of activation in comparison to those located in other zones. This has only been described in large muscles whose morphology proves the existence of a FC. However, there is no background information about small muscles, such as the Abductor digiti minimi manus (ADM). The objective of this study was to compare the activation of the MU in different zones of the ADM to support the hypothesis of the existence of a FC in the ADM. By using a cross- sectional, analytical, observational study, the activity of the MUs in the ADM was assessed in 12 volunteers (age 21 ± 1.6 years old; weight 75.3 ± 8 kg; height 176.2 ± 7.3 cm; average ± standard deviation). The activity of MUs was evaluated using high-density surface electromyography (HD-sEMG) with an array of 64 electrodes arranged two-dimensionally. This allowed us to record the activity of the MUs in three zones of the ADM (Z1: dorsal zone; Z2: dorsal-palmar zone and Z3: palmar zone). Electromyographic recordings were obtained during voluntary isometric contractions of the ADM at 20, 40, 60 and 80 % of the maximum voluntary contraction (MVC). The comparison of the activation levels of MUs between the three zones was carried out using a mixed model analysis of covariance. The results showed a significant difference between the dorsal and palmar zones at 40 % of the MVC (p= 0.03), and between the dorsal and dorsal- palmar zone at 80 % of the MVC (p= 0.03). The results obtained in the evaluated sample support the hypothesis of the existence of FC in the ADM. However, further research is needed to determine with greater certainty the presence of this compartmentalisation in the ADM.

RESUMEN: Existe evidencia que demuestra la presencia de una compartimentalización funcional (CF) en algunos músculos esqueléticos. Aquello se traduce en que las unidades motoras (UM) agrupadas en ciertas zonas del músculo, presentan diferentes niveles de activación a las ubicadas en otras regiones. Esto solo ha sido descrito en músculos grandes, cuya morfología justifica la existencia de una CF. Sin embargo, no existen antecedentes de aquello en músculos pequeños, tales como el abductor digiti minimi manus (ADM). El objetivo de este estudio fue comparar la activación de las UM en distintas zonas del ADM, con la finalidad sostener la hipótesis de la existencia de una CF en el ADM. Mediante un estudio observacional analítico transversal se evaluó la actividad de las UM del ADM en 12 voluntarios (edad 21±1,6 años; peso 75,3±8 kg; altura 176,2 ± 7,3 cm; promedio ± desviación estándar). La actividad de las UM, se evaluó mediante electromiografía de superficie alta densidad usando una matriz de 64 electrodos dispuestos bidimensionalmente. Esta permitió registrar la actividad de las UM en tres zonas del ADM (Z1: zona dorsal; Z2: zona dorso-palmar y Z3: zona palmar). Los registros electromiográficos fueron obtenidos durante contracciones isométricas voluntarias del ADM al 20, 40, 60 y 80 % de la contracción voluntaria máxima (CVM). La comparación de los niveles de activación de las UM entre las tres zonas fue realizada mediante un análisis de modelos mixtos de covarianza. Los resultados indicaron que existió diferencia significativa entre la zona dorsal y palmar al 40 % de la CVM (p=0,03), y entre la zona dorsal y dorso-palmar al 80 % de la CVM (p=0,03). Los resultados obtenidos en la muestra evaluada sostienen la hipótesis de la existencia de una CF en el ADM. Sin embargo, son necesarias más investigaciones para establecer con mayor certeza la presencia de esta compartimentalización en el ADM.

Neuromuscular compartmentalization of the vastus medialis muscle: comparison of the activity of the vastus medialis obliquus and the vastus medialis longus by high density electromyography / Compartimentación neuromuscular del músculo vasto medial: comparación de la actividad del vasto medial oblicuo y del vasto medial largo mediante electromiografía de alta densidad

SUMMARY: Anatomical studies describe the vastus medialis (VM) as being subdivided into two morphologically distinct components, the vastus medialis obliquus (VMO) and the vastus medialis longus (VML). However, there are discrepancies regarding the functional differentiation of these components. The aim of this study was to compare the levels of activation of the VMO and the VML by high density surface electromyography. Twelve healthy young women (age: 21.4 ± 2.0 years; weight: 58.1 ± 7.5 kg; height: 1.6 ± 0.1 m), performed an open kinetic chain knee exercise during which the EMG activity of the VMO and the VML was recorded with two- dimensional matrices of 32 surface electrodes. The exercises were performed with three levels of resistance (5, 10 and 15 % of the body weight (BW)), considering three phases: concentric, isometric and excentric. In the isometric phase the VMO had greater activation than the VML with the three levels of resistance (p<0.05). In the excentric phase, the VMO also showed greater activation than the VML with the 10 and 15 % BW resistance levels, while in the concentric phase, the VMO showed greater activity than the VML with only the 15 % BW resistance. The results indicated significant differences in the activation level of the two components of the VM. This bears importance in the development of exercises intended to achieve a greater or more selective activation of the VMO. In the sample subjected to evaluation, the EMG recordings describe a greater activation of the VMO in comparison to the VML, which is more important in the isometric and excentric phases of the flexion/extension of the knee in an open kinetic chain. These findings suggest a functional compartmentalization of the VM.

RESUMEN: Los estudios anatómicos describen que el músculo vasto medial (VM) se subdivide en dos componentes morfológicamente distintos, el vasto medial obliquus (VMO) y el vasto medial largo (VML). Sin embargo, existen discrepancias con respecto a la diferenciación funcional de estos componentes. El objetivo de este estudio fue comparar los niveles de activación del VMO y el VML mediante electromiografía de superficie de alta densidad. Doce mujeres jóvenes sanas (edad: 21,4 ± 2,0 años; peso: 58,1 ± 7,5 kg; altura: 1,6 ± 0,1 m), realizaron un ejercicio de rodilla de cadena cinética abierta durante el cual se registró la actividad EMG de la VMO y la VML con dos matrices dimensionales de 32 electrodos de superficie. Los ejercicios se realizaron con tres niveles de resistencia (5, 10 y 15% del peso corporal (PC)), considerando tres fases: concéntrica, isométrica y excéntrica. En la fase isométrica el VMO tuvo mayor activación que el VML con los tres niveles de resistencia (p <0,05). En la fase excéntrica, el VMO también mostró mayor activación que el VML con los niveles de resistencia de 10 y 15% BW, mientras que en la fase concéntrica, el VMO mostró mayor actividad que el VML con solo el 15 % de resistencia al BW. Los resultados indicaron diferencias significativas en el nivel de activación de los dos componentes de la VM. Esto tiene importancia en el desarrollo de ejercicios destinados a lograr una activación mayor o más selectiva del VMO. En la muestra sometida a evaluación, los registros EMG describen una mayor activación del VMO en comparación con el VML, que es más importante en las fases isométrica y excéntrica de la flexión / extensión de la rodilla en cadena cinética abierta. Estos hallazgos sugieren una compartimentación funcional de la VM.