Universität zu Köln

Christopher, Andrea, Hameister, Heike, Corrigall, Holly, Ebenhoeh, Oliver, Mueller, Berndt and Ullner, Ekkehard (2016). Modelling Robust Feedback Control Mechanisms That Ensure Reliable Coordination of Histone Gene Expression with DNA Replication. PLoS One, 11 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Histone proteins are key elements in the packing of eukaryotic DNA into chromosomes. A little understood control system ensures that histone gene expression is balanced with DNA replication so that histone proteins are produced in appropriate amounts. Disturbing or disrupting this system affects genome stability and gene expression, and has detrimental consequences for human development and health. It has been proposed that feedback control involving histone proteins contributes to this regulation and there is evidence implicating cell cycle checkpoint molecules activated when DNA synthesis is impaired in this control. We have developed mathematical models that incorporate these control modes in the form of inhibitory feedback of histone gene expression from free histone proteins, and alternatively a direct link that couples histone RNA synthesis to DNA synthesis. Using our experimental evidence and related published data we provide a simplified description of histone protein synthesis during S phase. Both models reproduce the coordination of histone gene expression with DNA replication during S phase and the down-regulation of histone RNA when DNA synthesis is interrupted, but only the model incorporating histone protein feedback control was able to effectively simulate the coordinate expression of a simplified histone gene family. Our combined theoretical and experimental approach supports the hypothesis that the regulation of histone gene expression involves feedback control.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Christopher, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Hameister, Heike UNSPECIFIED UNSPECIFIED UNSPECIFIED Corrigall, Holly UNSPECIFIED UNSPECIFIED UNSPECIFIED Ebenhoeh, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Berndt UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullner, Ekkehard UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-258097
DOI:	10.1371/journal.pone.0165848
Journal or Publication Title:	PLoS One
Volume:	11
Number:	10
Date:	2016
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LOOP BINDING-PROTEIN; MESSENGER-RNA METABOLISM; HELA-CELL CYCLE; S-PHASE; TRIGGERS DEGRADATION; MAMMALIAN-CELLS; IN-VITRO; U7 SNRNP; HINF-P; SLBP Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25809