Reference: Holbert MA, et al. (2007) The human monocytic leukemia zinc finger histone acetyltransferase domain contains DNA-binding activity implicated in chromatin targeting. J Biol Chem 282(50):36603-13

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Abstract


The human monocytic leukemia zinc finger (MOZ) protein is an essential transcriptional coactivator and histone acetyltransferase (HAT) that plays a primary role in the differentiation of erythroid and myeloid cells and is required to maintain hematopoietic stem cells. Chromosomal translocations involving the HAT-encoded region are also associated with acute myeloid leukemia. Here we present the x-ray crystal structure of the MOZ HAT domain and related biochemical studies. We find that the HAT domain contains a central region that is structurally and functionally conserved with the yeast MYST HAT protein Esa1, but contains more divergent N- and C-terminal regions harboring a TFIIIA-type zinc finger and helix-turn-helix DNA-binding motifs. Solution DNA-binding and acetyltransferase activity assays, in concert with mutagenesis, confirm that the MOZ HAT domain binds strongly to DNA through the zinc finger and helix-turn-helix motifs and that DNA binding and catalysis are not mutually exclusive. Consistent with the DNA-binding properties of MOZ, we also show that MOZ is able to acetylate nucleosomes and free histones equally well, whereas other HATs prefer free histones. Our results reveal, for the first time, that enzymatic and DNA-targeting activities can be contained within the same chromatin regulatory domain.

Reference Type
Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov't
Authors
Holbert MA, Sikorski T, Carten J, Snowflack D, Hodawadekar S, Marmorstein R
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