Two independent modes of chromatin organization revealed by cohesin removal

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Schwarzer, W (Autor) Outra; Abdennur, N (Autor) Outra; Goloborodko, A (Autor) Outra; Pekowska, A (Autor) Outra; Fudenberg, G (Autor) Outra; Loe Mie, Y (Autor) Outra; Nuno A Fonseca (Autor) Outra; Huber, W (Autor) Outra; Haering, CH (Autor) Outra; Mirny, L (Autor) Outra; Spitz, F (Autor) Outra

Revista

Título: Nature

Vol. 551

Páginas: 51-56

ISSN: 0028-0836

Editora: Springer Nature

Indexação

Scopus - 328 Citações

Outras Informações

ID Authenticus: P-00N-6ZZ

DOI: 10.1038/nature24281

Abstract (EN): Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.

Idioma: Inglês

Tipo (Avaliação Docente): Científica