RESUMO
3D genome organization regulates gene expression in different physiological and pathological contexts. Characterization of chromatin structure at different scales has provided information about how the genome organizes in the nuclear space, from chromosome territories, compartments of euchromatin and heterochromatin, topologically associated domains to punctual chromatin loops between genomic regulatory elements and gene promoters. In recent years, chromosome conformation capture technologies have also been used to characterize structural variations (SVs) de novo in pathological conditions. The study of SVs in cancer, has brought information about transcriptional misregulation that relates directly to the incidence and prognosis of the disease. For example, gene fusions have been discovered arising from chromosomal translocations that upregulate oncogenes expression, and other types of SVs have been described that alter large genomic regions encompassing many genes. However, studying SVs in 2D cannot capture all their regulatory implications in the genome. Recently, several bioinformatic tools have been developed to identify and classify SVs from chromosome conformation capture data and clarify how they impact chromatin structure in 3D, resulting in transcriptional misregulation. Here, we review recent literature concerning bioinformatic tools to characterize SVs from chromosome conformation capture technologies and exemplify their vast potential to rebuild the 3D landscape of genomes in cancer. The study of SVs from the 3D perspective can produce essential information about drivers, molecular targets, and disease evolution.
RESUMO
Lamins are components of the nuclear lamina, a protein meshwork that underlies the nuclear membrane. Lamins interact with chromatin in transcriptionally silent regions defined as lamina-associated-domains (LADs). However, recent studies have shown that lamins regulate active transcription inside LADs. In addition, ChIP-seq analysis has shown that lamins interact with lamin-dependent promoters and enhancers located in the interior of the nucleus. Moreover, functional studies suggest that lamins regulate transcription at associated-promoters and long-range chromatin interactions of key developmental gene programs. This review will discuss emerging, non-canonical functions of lamins in controlling non-silent genes located both inside and outside of LADs, focusing on transcriptional regulation and chromatin organization in Drosophila and mammals as metazoan model organisms.
Assuntos
Cromatina , Lâmina Nuclear , Animais , Núcleo Celular/metabolismo , Cromatina/metabolismo , Laminas/genética , Laminas/metabolismo , Mamíferos/genética , Membrana Nuclear/metabolismo , Lâmina Nuclear/metabolismoRESUMO
The spatial organization of the chromatinized genome inside the cell nucleus impacts genomic function. In transcription, the hierarchical genome structure creates spatial regulatory landscapes, in which modulating elements like enhancers can contact their target genes and activate their expression, as a result of restricting their exploration to a specific topological neighbourhood. Here we describe exciting recent findings obtained through "C" technologies in pluripotent cells and early embryogenesis and emphasize some of the key unanswered questions arising from them.