We developed a general approach that combines chromosome conformation capture carbon copy (5C) with the Integrated Modeling Platform (IMP) to generate high-resolution three-dimensional models of chromatin at the megabase scale. We applied this approach to the ENm008 domain on human chromosome 16, containing the α-globin locus, which is expressed in K562 cells and silenced in lymphoblastoid cells (GM12878). The models accurately reproduce the known looping interactions between the α-globin genes and their distal regulatory elements. Further, we find using our approach that the domain folds into a single globular conformation in GM12878 cells, whereas two globules are formed in K562 cells. The central cores of these globules are enriched for transcribed genes, whereas nontranscribed chromatin is more peripheral. We propose that globule formation represents a higher-order folding state related to clustering of transcribed genes around shared transcription machineries, as previously observed by microscopy. © 2011 Nature America, Inc. All rights reserved.

Baú, D., Sanyal, A., Lajoie, B.R., Capriotti, E., Byron, M., Lawrence, J.B., et al. (2011). The three-dimensional folding of the α-globin gene domain reveals formation of chromatin globules. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 18(1), 107-115 [10.1038/nsmb.1936].

The three-dimensional folding of the α-globin gene domain reveals formation of chromatin globules

CAPRIOTTI, EMIDIO;
2011

Abstract

We developed a general approach that combines chromosome conformation capture carbon copy (5C) with the Integrated Modeling Platform (IMP) to generate high-resolution three-dimensional models of chromatin at the megabase scale. We applied this approach to the ENm008 domain on human chromosome 16, containing the α-globin locus, which is expressed in K562 cells and silenced in lymphoblastoid cells (GM12878). The models accurately reproduce the known looping interactions between the α-globin genes and their distal regulatory elements. Further, we find using our approach that the domain folds into a single globular conformation in GM12878 cells, whereas two globules are formed in K562 cells. The central cores of these globules are enriched for transcribed genes, whereas nontranscribed chromatin is more peripheral. We propose that globule formation represents a higher-order folding state related to clustering of transcribed genes around shared transcription machineries, as previously observed by microscopy. © 2011 Nature America, Inc. All rights reserved.
2011
Baú, D., Sanyal, A., Lajoie, B.R., Capriotti, E., Byron, M., Lawrence, J.B., et al. (2011). The three-dimensional folding of the α-globin gene domain reveals formation of chromatin globules. NATURE STRUCTURAL & MOLECULAR BIOLOGY, 18(1), 107-115 [10.1038/nsmb.1936].
Baú, Davide; Sanyal, Amartya; Lajoie, Bryan R.; Capriotti, Emidio; Byron, Meg; Lawrence, Jeanne B.; Dekker, Job; Marti-Renom, Marc A
File in questo prodotto:
Eventuali allegati, non sono esposti

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/564940
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 151
  • Scopus 238
  • ???jsp.display-item.citation.isi??? 221
social impact