A proteomics study identifying interactors of the FSHD2 gene product SMCHD1 reveals RUVBL1-dependent DUX4 repression

Structural Maintenance of Chromosomes Hinge Domain Containing 1 (SMCHD1) is a chromatin repressor, which is mutated in > 95% of Facioscapulohumeral dystrophy (FSHD) type 2 cases. In FSHD2, SMCHD1 mutations ultimately result in the presence of the cleavage stage transcription factor DUX4 in muscle cells due to a failure in epigenetic repression of the D4Z4 macrosatellite repeat on chromosome 4q, which contains the DUX4 locus. While binding of SMCHD1 to D4Z4 and its necessity to maintain a repressive D4Z4 chromatin structure in somatic cells are well documented, it is unclear how SMCHD1 is recruited to D4Z4, and how it exerts its repressive properties on chromatin. Here, we employ a quantitative proteomics approach to identify and characterize novel SMCHD1 interacting proteins, and assess their functionality in D4Z4 repression. We identify 28 robust SMCHD1 nuclear interactors, of which 12 are present in D4Z4 chromatin of myocytes. We demonstrate that loss of one of these SMCHD1 interacting proteins, RuvB-like 1 (RUVBL1), further derepresses DUX4 in FSHD myocytes. We also confirm the interaction of SMCHD1 with EZH inhibitory protein (EZHIP), a protein which prevents global H3K27me3 deposition by the Polycomb repressive complex PRC2, providing novel insights into the potential function of SMCHD1 in the repression of DUX4 in the early stages of embryogenesis. The SMCHD1 interactome outlined herein can thus provide further direction into research on the potential function of SMCHD1 at genomic loci where SMCHD1 is known to act, such as D4Z4 repeats, the inactive X chromosome, autosomal gene clusters, imprinted loci and telomeres.Cancer Signaling networks and Molecular Therapeutic

Difficulties of radiological diagnosis оf small breast cancers

Introduction. Breast cancer in the structure of malignancies in women takes the 1st place. There has been an annual increase in morbidity, including due to improvements in diagnostic interventions and screening. Mammography and ultrasound of the breasts is mandatory when diagnosing breast cancer. The difficulties of diagnosis are revealed in small tumorsВведение. Рак молочной железы (РМЖ) в структуре злокачественных новообразований (ЗНО) у женщин занимает первое место. Отмечается ежегодный прирост заболеваемости, в том числе из-за усовершенствования диагностических мероприятий и скрининга. Маммография и ультразвуковое исследование молочных желез является обязательным при постановке диагноза РМЖ. Сложности диагностики выявляются при опухолях малых размеров