Conservation of the MORF4 related gene family: identification of a new chromo domain subfamily and novel protein motif

The seven member, human MORF4 related gene (MRG) family was recently identi fied based on the ability of Mortality factor on chromosome 4 (MORF4) to in duce replicative senescence in immortal cell lines assigned to complementat ion group B (Bertram et al., 1999, Mel. Cell Biol. 19, 1;179- 1485). Initia l computer based similarity searches identified human retinoblastoma bindin g protein 1 (RBP-1), Drosophila melanognster male specific lethal-3 (Msl-3) , S, pombe altered polarity-13 (Alp13) and S. cerevisiae Eaf3p, a component of the yeast NuA4 HAT complex (Galarneau et al,, 2000. Mel. Cell 5, 927-93 7), as having similarity to the human MRG protein family. This suggested th at the MRG family might be found in multiple species, and analysis of other homologs would provide functional and evolutionary insights into this gene family. Here, we report that MRG family members are present in twenty-thre e species based on molecular assays and sequence similarity searches. The n ew family members were divided into two groups based on similarity to the p redominant human MRC family members, MRG15 and MRGX. The family members sim ilar to MRC 15 define a new, highly conserved subsection of the chrome doma in superfamily. Additionally, conservation in the C-terminal two thirds of all the MRG family members and the Drosophila and human MSL-3 proteins defi nes a new protein domain, the MRG domain. These results indicate a highly c onserved role for the MRG family in transcriptional regulation via chromati n remodeling by histone acetylation. (C) 2001 Elsevier Science B.V. All rig hts reserved.