LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex.

BACKGROUND: Long Interspersed Nuclear Element-1 (L1) is an oncogenic mammalian retroelement silenced early in development via tightly controlled epigenetic mechanisms. We have previously shown that the regulatory region of human and murine L1s interact with retinoblastoma (RB) proteins to effect retroelement silencing. The present studies were conducted to identify the corepressor complex responsible for RB-mediated silencing of L1. METHODS: Chromatin immunoprecipitation and silencing RNA technology were used to identify the repressor complex that silences L1 in human and murine cells. RESULTS: Components of the Nucleosomal and Remodeling Deacetylase (NuRD) multiprotein complex specifically enriched the L1 5'-untranslated DNA sequence in human and murine cells. Genetic ablation of RB proteins in murine cells destabilized interactions within the NuRD macromolecular complex and mediated nuclear rearrangement of Mi2-ß, an ATP-dependent helicase subunit with nucleosome remodeling activity. Depletion of Mi2-ß, RbAP46 and HDAC2 reduced the repressor activity of the NuRD complex and reactivated a synthetic L1 reporter in human cells. Epigenetic reactivation of L1 in RB-null cells by DNA damage was markedly enhanced compared to wild type cells. CONCLUSIONS: RB proteins stabilize interactions of the NuRD corepressor complex within the L1 promoter to effect L1 silencing. L1 retroelements may serve as a scaffold on which RB builds heterochromatic regions that regulate chromatin function.

Cystic adnexal mass in a 16-year-old female: Ovarian pathology or complication of a Müllerian anomaly?

Patient: Female, 16 Final Diagnosis: Pelvic mass Symptoms: None Medication: None Clinical Procedure: CT • MRI Specialty: Diagnostic radiology • pediatrics. OBJECTIVE: Unusual presentation of unknown etiology, Rare disease, Mistake in diagnosis. BACKGROUND: Müllerian anomalies encompass a wide variety of malformations in the female genital tract, usually associated with renal and anorectal malformations. Of these anomalies, approximately 11% are uterus didelphys, which occurs when midline fusion of the müllerian ducts is arrested to a variable extent. CASE REPORT: We report the case of a 16-year-old female with uterine didelphys, jejunal malrotation, hematometra, hematosalpinx, and bilateral subcentimeter homogenous circular cystic-like renal lesions, who initially presented with left lower quadrant abdominal pain, non-bloody vomiting, and a history of irregular menstrual periods. Initial CT was confusing for an adnexal cystic mass, but further imaging disclosed the above müllerian anomalies. CONCLUSIONS: Müllerian anomalies may mimic other, more common, adnexal lesions; thus, adequate evaluation of suspicious cystic adnexal masses with multiple and advanced imaging modalities such as MRI is essential for adequate diagnosis and management.