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Reprogramming of lysosomal gene expression by interleukin-4 and Stat6

Brignull, LM, Czimmerer, Z, Saidi, H, Daniel, B, Villela, I, Bartlett, NW, Johnston, SL, Meira, LB, Nagy, L and Nohturfft, A (2013) Reprogramming of lysosomal gene expression by interleukin-4 and Stat6 BMC GENOMICS, 14, ARTN 8.

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Abstract

Background: Lysosomes play important roles in multiple aspects of physiology, but the problem of how the transcription of lysosomal genes is coordinated remains incompletely understood. The goal of this study was to illuminate the physiological contexts in which lysosomal genes are coordinately regulated and to identify transcription factors involved in this control.Results: As transcription factors and their target genes are often co-regulated, we performed meta-analyses of array-based expression data to identify regulators whose mRNA profiles are highly correlated with those of a core set of lysosomal genes. Among the ~50 transcription factors that rank highest by this measure, 65% are involved in differentiation or development, and 22% have been implicated in interferon signaling. The most strongly correlated candidate was Stat6, a factor commonly activated by interleukin-4 (IL-4) or IL-13. Publicly available chromatin immunoprecipitation (ChIP) data from alternatively activated mouse macrophages show that lysosomal genes are overrepresented among Stat6-bound targets. Quantification of RNA from wild-type and Stat6-deficient cells indicates that Stat6 promotes the expression of over 100 lysosomal genes, including hydrolases, subunits of the vacuolar H+ ATPase and trafficking factors. While IL-4 inhibits and activates different sets of lysosomal genes, Stat6 mediates only the activating effects of IL-4, by promoting increased expression and by neutralizing undefined inhibitory signals induced by IL-4.Conclusions: The current data establish Stat6 as a broadly acting regulator of lysosomal gene expression in mouse macrophages. Other regulators whose expression correlates with lysosomal genes suggest that lysosome function is frequently re-programmed during differentiation, development and interferon signaling. © 2013 Brignull et al.; licensee BioMed Central Ltd.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Biochemical Sciences
Authors :
AuthorsEmailORCID
Brignull, LMUNSPECIFIEDUNSPECIFIED
Czimmerer, ZUNSPECIFIEDUNSPECIFIED
Saidi, HUNSPECIFIEDUNSPECIFIED
Daniel, BUNSPECIFIEDUNSPECIFIED
Villela, IUNSPECIFIEDUNSPECIFIED
Bartlett, NWUNSPECIFIEDUNSPECIFIED
Johnston, SLUNSPECIFIEDUNSPECIFIED
Meira, LBUNSPECIFIEDUNSPECIFIED
Nagy, LUNSPECIFIEDUNSPECIFIED
Nohturfft, AUNSPECIFIEDUNSPECIFIED
Date : 5 December 2013
Identification Number : 10.1186/1471-2164-14-853
Uncontrolled Keywords : Science & Technology, Life Sciences & Biomedicine, Biotechnology & Applied Microbiology, Genetics & Heredity, BIOTECHNOLOGY & APPLIED MICROBIOLOGY, GENETICS & HEREDITY, TRANSCRIPTION FACTOR, C57BL/6J MICE, MITOCHONDRIAL BIOGENESIS, ALTERNATIVE ACTIVATION, CYSTEINE CATHEPSINS, CELLULAR CLEARANCE, MODULE NETWORKS, SMALL-INTESTINE, RECEPTOR-ALPHA, BINDING-SITES
Related URLs :
Additional Information : © 2013 Brignull et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Depositing User : Symplectic Elements
Date Deposited : 06 Oct 2015 09:47
Last Modified : 06 Oct 2015 09:47
URI: http://epubs.surrey.ac.uk/id/eprint/808673

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