Originally published as Genetics Published Articles Ahead of Print on November 19, 2005.

Genetics, Vol. 172, 1069-1078, February 2006, Copyright © 2006
doi:10.1534/genetics.105.049957

High Mobility Group Proteins HMGD and HMGZ Interact Genetically With the Brahma Chromatin Remodeling Complex in Drosophila

Anan Ragab1, Elizabeth C. Thompson and Andrew A. Travers

MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom

1 Corresponding author: Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
E-mail: a.ragab{at}dkfz-heidelberg.de

Many pleiotropic roles have been ascribed to small abundant HMG–Box (HMGB) proteins in higher eukaryotes but their precise function has remained enigmatic. To investigate their function genetically we have generated a defined deficiency uncovering the functionally redundant genes encoding HMGD and HMGZ, the Drosophila counterparts of HMGB1–3 in mammals. The resulting mutant is a strong hypomorphic allele of HmgD/Z. Surprisingly this allele is viable and exhibits only minor morphological defects even when homozygous. However, this allele interacts strongly with mutants of the Brahma chromatin remodeling complex, while no interaction was observed with mutant alleles of other remodeling complexes. We also observe genetic interactions between the HmgD/Z deficiency and some, but not all, known Brahma targets. These include the homeotic genes Sex combs reduced and Antennapedia, as well as the gene encoding the cell-signaling protein Rhomboid. In contrast to more general structural roles previously suggested for these proteins, we infer that a major function of the abundant HMGB proteins in Drosophila is to participate in Brahma-dependent chromatin remodeling at a specific subset of Brahma-dependent promoters.