MYST family, HATs

HBOl Histone acetyltransferase bound to ORCl (origin-recognition complex subunit 1). A MYST family HAT involved in DNA replication. 

MOF Males-absent on the first. A MYST family HAT subunit of the Drosophila MSL dosage-compensation complex and a highly homologous human complex. 

MYST family HATs frequently fused to other proteins as a result of chromosomal translocation in acute myeloid leukemia. 

Tip60 Tat-interacting protein of 60kDa. A MYST family HAT, catalytic subunit of the NuA4 complex. Performs key functions in repair of double-stranded DNA breaks. 

This chapter focuses on the MYST family HATs, describes their functions in the many diverse nuclear processes and discusses the established and putative links between their activities and human disease. 

While all MYST family members possess intrinsic HAT activity, they do not function in isolation in vivo but, rather, are found in multisubunit protein complexes. Thus, to fully understand or to plausibly speculate about the potential roles of MYST HATs in disease, it is necessary to incorporate the known facts about other complex members. To this end, the sections of this chapter that discuss individual MYST HATs will also describe the complexes within which they function and summarize the available disease-related information about other complex components. 

The HATs belonging to the MYST family play essential roles in a wide variety of critical cellular processes. Further research will undoubtedly reveal additional functions of these enzymes that profoundly impact cellular growth, differentiation and replication. It is not surprising, therefore, that their malfunctions or subversion of their regular functions by cellular or viral machinery have been linked to a number of human diseases. A comprehensive understanding of these mechanisms is crucial to design of successful therapies, such as small-molecule inhibitors, that will be able to specifically target the undesirable activities of MYST HATs. 

Structure of a HAT from the p300/CBP family has been long awaited, since these enzymes have no sequence similarity with enzymes of the GNAT and MYST families. The structure of the p300 HAT domain was solved very recently in complex with a Lys-GoA bi-substrate inhibitor, which required a highly intricate expression and purification protocol in order to produce a protein amenable to crystallization studies [24]. Analysis of the structure revealed however that, despite no sequence conservation, a similar structural core is observed as for the GNAT and MYST... 

ING Inhibitor of growth. A family of tumour suppressors (INGl-5). ING3, 4 and 5 are found in multisubunit complexes with the Tip60, MOZ/MORF and HBOl MYST HATs. Function in a number of key cellular processes and are frequently inactivated in human cancer. 

MYST HATs A family of acetyltransferases named after its founding members MOZ, Ybf2/Sas3, Sas2 and Tip60. Human MYST HATs include MOZ, Tip60, MOZ/MORF, HBOl and MOF. 

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