ABSTRACT
We demonstrate a high-speed linear microelectromechanical systems (MEMS) phase modulator capable of random access scanning at 350 kHz, so that any state can be accessed in 2.9 µs from any other state. 670 scan lines with a .87 deg field of view (FOV) are demonstrated in a Fourier regime, with a projected far-field response of 660 lines with an 18 deg FOV after magnification.
ABSTRACT
Lysine methylation of histones is recognized as an important component of an epigenetic indexing system demarcating transcriptionally active and inactive chromatin domains. Trimethylation of histone H3 lysine 4 (H3K4me3) marks transcription start sites of virtually all active genes. Recently, we reported that the WD40-repeat protein WDR5 is important for global levels of H3K4me3 and control of HOX gene expression. Here we show that a plant homeodomain (PHD) finger of nucleosome remodelling factor (NURF), an ISWI-containing ATP-dependent chromatin-remodelling complex, mediates a direct preferential association with H3K4me3 tails. Depletion of H3K4me3 causes partial release of the NURF subunit, BPTF (bromodomain and PHD finger transcription factor), from chromatin and defective recruitment of the associated ATPase, SNF2L (also known as ISWI and SMARCA1), to the HOXC8 promoter. Loss of BPTF in Xenopus embryos mimics WDR5 loss-of-function phenotypes, and compromises spatial control of Hox gene expression. These results strongly suggest that WDR5 and NURF function in a common biological pathway in vivo, and that NURF-mediated ATP-dependent chromatin remodelling is directly coupled to H3K4 trimethylation to maintain Hox gene expression patterns during development. We also identify a previously unknown function for the PHD finger as a highly specialized methyl-lysine-binding domain.
Subject(s)
Chromatin Assembly and Disassembly , Chromosomal Proteins, Non-Histone/chemistry , Chromosomal Proteins, Non-Histone/metabolism , Histones/chemistry , Histones/metabolism , Lysine/metabolism , Adenosine Triphosphatases/metabolism , Amino Acid Motifs , Animals , Antigens, Nuclear , Epigenesis, Genetic , Gene Expression Regulation , Humans , Methylation , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Xenopus/embryology , Xenopus/growth & development , Xenopus/metabolismABSTRACT
The conserved histone variant H2AZ has an important role in the regulation of gene expression and the establishment of a buffer to the spread of silent heterochromatin. How histone variants such as H2AZ are incorporated into nucleosomes has been obscure. We have found that Swr1, a Swi2/Snf2-related adenosine triphosphatase, is the catalytic core of a multisubunit, histone-variant exchanger that efficiently replaces conventional histone H2A with histone H2AZ in nucleosome arrays. Swr1 is required for the deposition of histone H2AZ at specific chromosome locations in vivo, and Swr1 and H2AZ commonly regulate a subset of yeast genes. These findings define a previously unknown role for the adenosine triphosphate-dependent chromatin remodeling machinery.
