%0 Journal Article
%T A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding
%A Emily Ko
%A Dennis Ko
%A Carolyn Chen
%A Joseph S Lipsick
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-77
%X In vertebrates, c-Myb (MYB), A-Myb (MYBL1), and B-Myb (MYBL2) comprise the Myb gene family. Myb proteins encoded by these genes serve essential roles in transcriptional regulation and cell cycle control (reviewed in [1]). Studies of c-Myb null and hypomorphic mutant mice have delineated an essential role in hematopoiesis and in the maintenance of intestinal epithelium [2,3]. A-Myb null mutant mice display abnormal spermatogenesis and mammary gland proliferation [4]. B-Myb null mice suffer from embryonic lethality at the 8-cell stage, suggesting an essential role for B-Myb in cell proliferation that is consistent with the expression of B-Myb in all proliferating cell types [5]. Importantly, aberrant expression of these Myb genes occurs in a variety of human malignancies including leukemias, lymphomas, breast, colon, brain, pancreatic, and lung cancers (reviewed in [1]).Proteins in the Myb family share conservation of both an N-terminal DNA-binding domain (DBD) and a C-terminal regulatory domain. The Myb DBD is composed of three imperfect helix-turn-helix repeats and Myb-related proteins have one or more of these Myb-like repeats [6]. In plants, Myb-related repeats have been utilized in hundreds of DNA-binding transcription factors [7]. Other Myb-related proteins serve an assortment of nuclear functions, including chromatin remodeling (SWI3, RSC, ISWI), covalent histone modification (ADA2, NCoR), basal transcription (TFIIIB-B', SNAPC4), transcriptional silencing (REB1, TTF1, RAP1), telomere regulation (TAZ1, TRF1, TRF2, RAP1), and RNA splicing (CDC5). Surprisingly, some of these proteins have conserved Myb-like repeats, but do not utilize this domain to bind DNA [1,6]. Deletion and mutational analysis of such Myb-related repeats has implicated these domains in histone binding [8-11].While it is tempting to think of DNA-binding domains (DBDs) of proteins as specialized building blocks with a singular DNA-binding function, the multifunctional nature of such domains has
%U http://www.molecular-cancer.com/content/7/1/77