PuSH - Publikationsserver des Helmholtz Zentrums München: High mobility group N proteins modulate the fidelity of the cellular transcriptional profile in a tissue- and variant-specific manner.

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Kugler, J.E.* ; Horsch, M. ; Huang, D.* ; Furusawa, T.* ; Rochman, M.* ; Garrett, L. ; Becker, L. ; Bohla, A. ; Hölter, S.M. ; Prehn, C. ; Rathkolb, B. ; Rácz, I.* ; Aguilar-Pimentel, J.A. ; Adler, T. ; Adamski, J. ; Beckers, J. ; Busch, D.H.* ; Eickelberg, O. ; Klopstock, T.* ; Ollert, M.* ; Stöger, T. ; Wolf, E.* ; Wurst, W. ; Yildirim, A.Ö. ; Zimmer, A.* ; Gailus-Durner, V. ; Fuchs, H. ; Hrabě de Angelis, M. ; Garfinkel, B.* ; Orly, Y.* ; Ovcharenko, I.* ; Bustin, M.*

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

J. Biol. Chem. 288, 16690-16703 (2013)

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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 the structure and function of chromatin, 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 Hmgn1-/-, Hmgn3-/-, and Hmgn5-/- 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 Hmgn-/- lines reveals very little overlap between the genes affected by the specific variants in the different tissues. Pathway analysis revels that loss of an HMGN variant affects subtly the expression of numerous genes in specific biological processes. We conclude 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.

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