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.The eukaryotic genome is packaged into chromatin, the highly organized DNA⅐protein complex that not only serves as a structural element in preserving genetic information but also as a dynamic scaffold from which nuclear processes occur such as transcription, replication, DNA repair, mitosis, and apoptosis (1, 2). The fundamental unit of chromatin is the nucleosome, consisting of 145-147 bp of DNA wrapped around an octameric histone core containing two molecules each of histone proteins H2A, H2B, H3, and H4. There are at least four types of protein domains that regulate DNA processes through chromatin modification. These include (a) enzymatic domains that either use ATP to translocate the DNA relative to the histone core proteins (3) or post-translationally modify the histone proteins (4, 5) and (b) non-enzymatic domains that recognize chromatin, either through interactions with unmodified or modified N-terminal histone tails or the DNA, or histone chaperone proteins that deposit histones or replace variant histones into chromatin. Many chromatin regulatory proteins often contain both an enzymatic and chromatin recognition domain, although, to date, there have been no reports of a single domain harboring both activities.Chromatin recognition domains that target histones include bromodomains (6, 7), which recognize specific acetyllysine modifications, chromodomains (8, 9), and tudor (10) domains, which bind specific methyllysine modifications, 14-3-3 domains, which recognize phosphoserine modifications (11), and SANT domains (12), which recognize unmodified histones. The SLIDE (12) and SWIRM (13, 14) domains are chromatin recognition modules that can target the DNA within nucleosomes.Among the enzymes that medi...

Translational control of gene expression is essential for development in organisms that rely on maternal mRNAs. In Drosophila, translation of maternal nanos (nos) mRNA must be restricted to the posterior of the early embryo for proper patterning of the anterior-posterior axis. Spatial control of nos translation is coordinated through the localization of a small subset of nos mRNA to the posterior pole late in oogenesis, activation of this localized mRNA, and repression of the remaining unlocalized nos mRNA throughout the bulk cytoplasm. Translational repression is mediated by the interaction of a cis-acting element in the nos 39 untranslated region with two proteins, Glorund (Glo) and Smaug (Smg), that function in the oocyte and embryo, respectively. The mechanism of Glo-dependent repression is unknown. Previous work suggests that Smg represses translation initiation but this model is not easily reconciled with evidence for polysome association of repressed nos mRNA. Using an in vitro translation system, we have decoupled translational repression of nos imposed during oogenesis from repression during embryogenesis. Our results suggest that both Glo and Smg regulate translation initiation, but by different mechanisms. Furthermore, we show that, during late oogenesis, nos translation is also repressed post-initiation and provide evidence that Glo mediates this event. This post-initiation block is maintained into embryogenesis during the transition to Smg-dependent regulation. We propose that the use of multiple modes of repression ensures inactivation of nos RNA that is translated at earlier stages of oogenesis and maintenance of this inactivate state throughout late oogenesis into embryogenesis.

Background: The nuclear receptors of the NR2E class play important roles in pattern formation and nervous system development. Based on a phylogenetic analysis of DNA-binding domains, we define two conserved groups of orthologous NR2E genes: the NR2E1 subclass, which includes C. elegans nhr-67, Drosophila tailless and dissatisfaction, and vertebrate Tlx (NR2E2, NR2E4, NR2E1), and the NR2E3 subclass, which includes C. elegans fax-1 and vertebrate PNR (NR2E5, NR2E3). PNR and Tll nuclear receptors have been shown to bind the hexamer half-site AAGTCA, instead of the hexamer AGGTCA recognized by most other nuclear receptors, suggesting unique DNA-binding properties for NR2E class members.

Effective communication is a requisite skill for scientists. However, formalized training in this area is often unavailable for members of the scientific community. As one approach to combat this problem, the American Society for Biochemistry and Molecular Biology (ASBMB) developed The Art of Science Communication, an eight-week-long online course that provides facilitated instruction on how to communicate science in an oral format. The course is offered three times a year, and as of December 2017, nearly 200 individuals from all career stages have taken part in it. The course completion rate is currently 60%, a rate three to five times as high as the average for similar Massive Open Online Courses (MOOCs). Participants have indicated that taking the course has improved their ability to communicate about their research, and that the skills and lessons learned have benefited them professionally. Moving forward, we are examining approaches that will help us improve the course and expand its reach throughout the scientific community. This article details the development of the course and examines the role and potential of such training within the larger scientific community.