RESUMEN
To infer potential causal relationships between 3D chromatin structure, enhancers, and gene transcription, we mapped each feature in a genome-wide fashion across eight narrowly spaced time points of macrophage activation. Enhancers and genes connected by loops exhibit stronger correlations between histone H3K27 acetylation and expression than can be explained by genomic distance or physical proximity alone. At these looped enhancer-promoter pairs, changes in acetylation at distal enhancers precede changes in gene expression. Changes in gene expression exhibit a directional bias at differential loop anchors; gained loops are associated with increased expression of genes oriented away from the center of the loop, and lost loops are often accompanied by high levels of transcription within the loop boundaries themselves. These results are consistent with a reciprocal relationship where loops can facilitate increased transcription by connecting promoters to distal enhancers, whereas high levels of transcription can impede loop formation.
Asunto(s)
Cromatina , Genómica , Regiones Promotoras Genéticas/genética , Acetilación , Elementos de Facilitación Genéticos/genéticaRESUMEN
PURPOSE: The purpose of this study was to compare clinical outcomes of segmental resection to lobectomy as increasing antenatal diagnosis of congenital pulmonary malformations has led to a shift in surgical management. METHODS: A retrospective institutional review for patients undergoing surgical excision of congenital pulmonary malformations was performed. RESULTS: Sixty-two patients with congenital pulmonary malformations were reviewed between 2001 and 2012. Forty-five were included for analysis. Malformations were subdivided into two groups, including congenital lobar emphysema (CLE) (n=11, 24%) and intrapulmonary (IP) lesions (n=34, 76%). Nineteen (56%) IP patients underwent segmental resection, and 15 (79%) were performed thoracoscopically without conversion to thoracotomy. None of these patients had recurrent disease. Lobectomy was performed in 11 (100%) CLE and 15 (44%) IP patients, and the majority were by thoracotomy. Median hospital stay was longer for the lobectomy group at 7days when compared to the segmentectomy group at 2days (p<0.001). There was not a difference in complication rate (21% vs. 19%, p=1.000) or in median number of chest tube days (2 vs. 3days, p=0.079) for segmentectomy versus lobectomy patients. CONCLUSIONS: Segmental resections of congenital pulmonary malformations can be performed safely while conserving healthy lung tissue.