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Set2-mediated methylation of histone H3 at Lys 36 (H3K36me) is a co-transcriptional event that is necessary for the activation of the Rpd3S histone deacetylase complex, thereby maintaining the coding region [...]

Vertebrae are derived from embryonic structures called somites, which form in a synchronized and rhythmic fashion from the presomitic mesoderm (PSM). Somite formation involves a molecular oscillator, called the segmentation [...], One of the most notable features of the vertebrate body plan organization is its bilateral symmetry, evident at the level of vertebrae and skeletal muscles. Here we show that a mutation in Rere (also known as atrophin2) leads to the formation of asymmetrical somites in mouse embryos, similar to embryos deprived of retinoic acid (1-4). Furthermore, we also demonstrate that Rere controls retinoic acid signalling, which is required to maintain somite symmetry by interacting with Fgf8 in the left-right signalling pathway. Rere forms a complex with Nr2f2, p300 (also known as Ep300) and a retinoic acid receptor, which is recruited to the retinoic acid regulatory element of retinoic acid targets, such as the Rarb promoter. Furthermore, the knockdown of Nr2f2 and/or Rere decreases retinoic acid signalling, suggesting that this complex is required to promote transcriptional activation of retinoic acid targets. The asymmetrical expression of Nr2f2 in the presomitic mesoderm overlaps with the asymmetry of the retinoic acid signalling response, supporting its implication in the control of somitic symmetry. Misregulation of this mechanism could be involved in symmetry defects of the human spine, such as those observed in patients with scoliosis.

A model system was used to show that the yeast SWI/SNF complex can place nucleosomes in an ATP-dependent reaction favouring the attachment of a histone octamer to an acceptor site on the same DNA molecule. SWI/SNF-mediated displacement is blocked by a barrie in the DNA, indicating that the repositioning involves sliding or tracking of nucleosomes along DNA.

There is a specific functional binding between the yeast activator Gcn4 or the VP16 activation domain with the Spt-Ada-Gcn5-acetyltransferase and NuA4 histone acetyltransferase (HAT) complexes. There is no interaction between the yeast HAT complexes Ada and NuA3, thus showing that the interaction of activator and HAT must be specific. It has been possible to demonstrate the targeting of native HAT complexes by a transcription-activation domain to nucleosomes to activate transcription.

Research shows how the malaria parasite Plasmodium falciparum manipulates the expression of its var genes to avoid recognition by the host immune system. Four experts comment on the implications of [...]

The TATA-binding protein (TBP) recognizes certain DNA sequences such as the TATA element in genes. There has been much discussion about how necessary the TBP-associated factors (TAFs) are for TBP to assemble and initiate transcription. Research papers now show a sub-group of TAF proteins may have a wider role in gene expression. In describing a transcriptional analysis of the yeast genome, TAF145 was found to be needed for transcription of approximately 16% of the genes. This implies TAFs are crucial for the expression of the majority of protein-coding genes.

Set2-mediated methylation of histone H3 at Lys?36 (H3K36me) is a co-transcriptional event that is necessary for the activation of the Rpd3S histone deacetylase complex, thereby maintaining the coding region of genes in a hypoacetylated state. In the absence of Set2, H3K36 or Rpd3S acetylated histones accumulate on open reading frames (ORFs), leading to transcription initiation from cryptic promoters within ORFs. Although the co-transcriptional deacetylation pathway is well characterized, the factors responsible for acetylation are as yet unknown. Here we show that, in yeast, co-transcriptional acetylation is achieved in part by histone exchange over ORFs. In addition to its function of targeting and activating the Rpd3S complex, H3K36 methylation suppresses the interaction of H3 with histone chaperones, histone exchange over coding regions and the incorporation of new acetylated histones. Thus, Set2 functions both to suppress the incorporation of acetylated histones and to signal for the deacetylation of these histones in transcribed genes. By suppressing spurious cryptic transcripts from initiating within ORFs, this pathway is essential to maintain the accuracy of transcription by RNA polymerase?II. [ABSTRACT FROM AUTHOR]