High mobility group N proteins modulate the fidelity of the cellular transcriptional profile in a tissue- and variant-specific manner

Jamie E. Kugler, Marion Horsch, Di Huang, Takashi Furusawa, Mark Rochman, Lillian Garrett, Lore Becker, Alexander Bohla, Sabine M. Hölter, Cornelia Prehn, Birgit Rathkolb, Ildikó Racz, Juan Antonio Aguilar-Pimentel, Thure Adler, Jerzy Adamski, Johannes Beckers, Dirk H. Busch, Oliver Eickelberg, Thomas Klopstock, Markus OllertTobias Stog̈er, Eckhard Wolf, Wolfgang Wurst, Ali On̈der Yildirim, Andreas Zimmer, Valérie Gailus-Durner, Helmut Fuchs, Martin Hrabě De Angelis, Benny Garfinkel, Joseph Orly, Ivan Ovcharenko, Michael Bustina*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

The nuclei of most vertebrate cells contain members of the high mobility group N (HMGN) protein family, which bind specifically to nucleosome core particles and affect chromatin structure and function, including transcription. Here, we study the biological role of this protein family by systematic analysis of phenotypes and tissue transcription profiles in mice lacking functional HMGN variants. Phenotypic analysis of Hmgn1tm1/tm1, Hmgn 3tm1/tm1, and Hmgn5tm1/tm1 mice and their wild type littermates with a battery of standardized tests uncovered variant-specific abnormalities. Gene expression analysis of four different tissues in each of the Hmgntm1/tm1 lines reveals very little overlap between genes affected by specific variants in different tissues. Pathway analysis reveals that loss of an HMGN variant subtly affects expression of numerous genes in specific biological processes.Weconclude that within the biological framework of an entire organism, HMGNs modulate the fidelity of the cellular transcriptional profile in a tissue- and HMGN variant-specific manner.

Original languageEnglish
Pages (from-to)16690-16703
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number23
DOIs
Publication statusPublished - 7 Jun 2013
Externally publishedYes

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