A biophysical model for transcription factories.

Authors:
Shamit Soneji
Shamit Soneji
Weatherall Institute of Molecular Medicine
United Kingdom
Tariq Enver
Tariq Enver
University College London
United Kingdom
Veronica J Buckle
Veronica J Buckle
Weatherall Institute of Molecular Medicine
United Kingdom
Francisco J Iborra
Francisco J Iborra
Weatherall Institute of Molecular Medicine
United Kingdom

BMC Biophys 2013 Feb 9;6. Epub 2013 Feb 9.

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

Summary: 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.

Download full-text PDF

Source
http://digital.csic.es/bitstream/10261/66749/4/2046-1682-6-2
Web SearchFound
http://www.biomedcentral.com/2046-1682/6/2
Publisher SiteFound
http://dx.doi.org/10.1186/2046-1682-6-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740778PMC
February 2013
10 Reads

Publication Analysis

Top Keywords

transcription factories
16
h4k16ac chromatin
12
chromatin
9
h4k16ac
5
transcription
5
separation microdomains
4
h4k16ac genes
4
body gene
4
entire body
4
gene h4k16ac
4
genes cluster
4
500 alternating
4
regions 500
4
phase separation
4
cluster regions
4
microdomains consistent
4
spans entire
4
factories
4
h4k16ac single
4
lysine h4k16ac
4

Similar Publications

Genome-wide distribution of histone H4 Lysine 16 acetylation sites and their relationship to gene expression.

Genome Integr 2013 Apr 12;4(1). Epub 2013 Apr 12.

Department of Radiation Oncology, Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Background: Histone post-translational modifications are critical determinants of chromatin structure and function, impacting multiple biological processes including DNA transcription, replication, and repair. The post-translational acetylation of histone H4 at lysine 16 (H4K16ac) was initially identified in association with dosage compensation of the Drosophila male X chromosome. However, in mammalian cells, H4K16ac is not associated with dosage compensation and the genomic distribution of H4K16ac is not precisely known. Read More

View Article
April 2013

A dual role for the histone methyltransferase PR-SET7/SETD8 and histone H4 lysine 20 monomethylation in the local regulation of RNA polymerase II pausing.

J Biol Chem 2014 Mar 23;289(11):7425-37. Epub 2014 Jan 23.

From the Department of Radiation Oncology and the Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia 30322.

RNA polymerase II (Pol II) promoter-proximal pausing plays a critical role in postinitiation transcriptional regulation at many metazoan genes. We showed recently that histone H4 lysine 16 acetylation (H4K16Ac), mediated by the MSL complex, facilitates the release of paused Pol II. In contrast, H4 lysine 20 trimethylation (H4K20me3), mediated by SUV420H2, enforces Pol II pausing by inhibiting MSL recruitment. Read More

View Article
March 2014

Role of hMOF-dependent histone H4 lysine 16 acetylation in the maintenance of TMS1/ASC gene activity.

Cancer Res 2008 Aug;68(16):6810-21

Department of Radiation Oncology and the Winship Cancer Institute, Emory University, Atlanta, Georgia 30322, USA.

Epigenetic silencing of tumor suppressor genes in human cancers is associated with aberrant methylation of promoter region CpG islands and local alterations in histone modifications. However, the mechanisms that drive these events remain unclear. Here, we establish an important role for histone H4 lysine 16 acetylation (H4K16Ac) and the histone acetyltransferase hMOF in the regulation of TMS1/ASC, a proapoptotic gene that undergoes epigenetic silencing in human cancers. Read More

View Article
August 2008

Islands of acetylated histone H4 in polytene chromosomes and their relationship to chromatin packaging and transcriptional activity.

J Cell Sci 1990 Jun;96 ( Pt 2):335-46

School of Basic Medical Sciences, Department of Anatomy, University of Birmingham Medical School, UK.

The four histones of the nucleosome core particle are all subject to enzyme-catalysed, post-translational acetylation at defined lysine residues in their amino-terminal domains. Much circumstantial evidence suggests a role for this process in modifying chromatin structure and function, but detailed mechanisms have not been defined. To facilitate studies on the functional significance of histone acetylation, we have prepared antibodies specific for the acetylated isoforms of histone H4. Read More

View Article
June 1990