Open Access Highly Accessed Research article

A biophysical model for transcription factories

Ana Z Canals-Hamann1, Ricardo Pires das Neves1, Joyce E Reittie1, Carlos Iñiguez2, Shamit Soneji1, Tariq Enver1, Veronica J Buckle1 and Francisco J Iborra13*

Author Affiliations

1 MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, UK

2 Departamento de Biotecnología, Universidad de Alicante, Alicante, 03080, Spain

3 Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, CSIC, Darwin 3, Campus de Canto Blanco, Madrid, 28049, Spain

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BMC Biophysics 2013, 6:2  doi:10.1186/2046-1682-6-2

Published: 9 February 2013

Abstract

Transcription factories are nuclear domains where gene transcription takes place although the molecular basis for their formation and maintenance are unknown. In this study, we explored how the properties of chromatin as a polymer may contribute to the structure of transcription factories. We found that transcriptional active chromatin contains modifications like histone H4 acetylated at Lysine 16 (H4K16ac). Single fibre analysis showed that this modification spans the entire body of the gene. Furthermore, H4K16ac genes cluster in regions up to 500 Kb alternating active and inactive chromatin. The introduction of H4K16ac in chromatin induces stiffness in the chromatin fibre. The result of this change in flexibility is that chromatin could behave like a multi-block copolymer with repetitions of stiff-flexible (active-inactive chromatin) components. Copolymers with such structure self-organize through spontaneous phase separation into microdomains. Consistent with such model H4K16ac chromatin form foci that associates with nascent transcripts. We propose that transcription factories are the result of the spontaneous concentration of H4K16ac chromatin that are in proximity, mainly in cis.

Keywords:
Epigenetics; Biophysics; H4K16Ac; BrUTP; Transcription Factories; RNA pol II; Nuclear organization