We describe a stable, multisubunit human histone acetyltransferase complex (hMSL) that contains homologs of the Drosophila dosage compensation proteins MOF, MSL1, MSL2, and MSL3. This complex shows strong specificity for histone H4 lysine 16 in chromatin in vitro, and RNA interference-mediated knockdown experiments reveal that it is responsible for the majority of H4 acetylation at lysine 16 in the cell. We also find that hMOF is a component of additional complexes, forming associations with host cell factor 1 and a protein distantly related to MSL1 (hMSL1v1). We find two versions of hMSL3 in the hMSL complex that differ by the presence of the chromodomain. Lastly, we find that reduction in the levels of hMSLs and acetylation of H4 at lysine 16 are correlated with reduced transcription of some genes and with a G 2 /M cell cycle arrest. This is of particular interest given the recent correlation of global loss of acetylation of lysine 16 in histone H4 with tumorigenesis.The dynamic regulation of chromatin structure can be brought about by a complex series of posttranslational modifications to histones, particularly on the amino-terminal histone tails (33,48). Among the lysines that can be acetylated, lysine 16 of histone H4 appears to be uniquely targeted in a number of organisms. Studies of telomeric silencing in Saccharomyces cerevisiae have shown that lysine 16-specific acetyltransferase and deacetylase activities determine the boundaries of silenced chromatin (32, 59). Furthermore, chromatin immunoprecipitation and site-directed mutagenesis in budding yeast clearly indicate that acetylation of H4 lysine 16 has an independent specific function in relation to gene transcription when compared to other histone acetylation sites (16,34). In Drosophila, lysine 16 acetylation is targeted to the hypertranscribed male X chromosome in the process of dosage compensation (8,35). Biochemical analysis of bulk histones in mammalian cells has indicated that most of the monoacetylated H4 is acetylated at lysine 16, as is most of the di-and triacetylated forms, leading to the suggestion that this is the first acetylation mark on H4 or possibly the last to be taken off (61, 69). One rationale for a special role for lysine 16 acetylation is that it is the only known site of acetylation in the basic patch of H4, a region from amino acids 16 to 20 that is implicated in the formation of higher-order chromatin structure (17). Recently, loss of acetylation at lysine 16 of histone H4 has been identified as a common hallmark of human cancer (22).In Drosophila, dosage compensation-the equalization of X-linked gene products in males and females-is achieved by enhancing the transcriptional level of X-linked genes in males.Five genes involved in this process were identified due to male-specific lethality when mutated (4,5,26). These genes are male-specific lethal 1 (msl1), msl2, msl3, maleless (mle), and males-absent on the first (mof). All five gene products form the MSL complex, which harbors histone acetyltransferase (HAT) activity with...

For the first time, large-area CVD-grown graphene films transferred onto flexible PET substrates were used as transparent conductive electrodes in alternating current electroluminescence (ACEL) devices. The flexible ACEL device based on a single-layer graphene electrode has a turn-on voltage of 80 V; at 480 V (16 kHz), the luminance and luminous efficiency are 1140 cd/m(2) and 5.0 lm/W, respectively. The turn-on voltage increases and the luminance decreases with increasing stacked layers of graphene, which means the single-layer graphene is the best optimal choice as the transparent conductive electrode. Furthermore, it demonstrates that the graphene-based ACEL device is highly flexible and can work very well even under a very large strain of 5.4%, suggesting great potential applications in flexible optoelectronics.

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