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Nucleosomal acetyltransferase of H4 (NuA4) is an essential transcriptional coactivator in eukaryotes, but remains poorly characterized in plants. Here, we describe Arabidopsis homologs of the NuA4 scaffold proteins Enhancer of Polycomb-Like 1 (AtEPL1) and Esa1-Associated Factor 1 (AtEAF1). Loss of AtEAF1 results in inhibition of growth and chloroplast development. These effects are stronger in the Atepl1 mutant and are further enhanced by loss of Golden2-Like (GLK) transcription factors, suggesting that NuA4 activates nuclear plastid genes alongside GLK. We demonstrate that AtEPL1 is necessary for nucleosomal acetylation of histones H4 and H2A.Z by NuA4 in vitro. These chromatin marks are diminished genome-wide in Atepl1, while another active chromatin mark, H3K9 acetylation (H3K9ac), is locally enhanced. Expression of many chloroplast-related genes depends on NuA4, as they are downregulated with loss of H4ac and H2A.Zac. Finally, we demonstrate that NuA4 promotes H2A.Z deposition and by doing so prevents spurious activation of stress response genes., Function of nucleosomal acetyltransferase of H4 (NuA4), one major complex of HAT, remains unclear in plants. Here, the authors generate mutants targeting two components of the putative NuA4 complex in Arabidopsis (EAF1 and EPL1) and show their roles in photosynthesis genes regulation through H4K5ac and H2A.Z acetylation.

Regulation of RNA polymerase II (Pol2) elongation in the promoter-proximal region is an important and ubiquitous control point for gene expression in metazoans. We report that transcription of the adenovirus 5 E4 region is regulated during the release of paused Pol2 into productive elongation by recruitment of the super-elongation complex, dependent on promoter H3K18/27 acetylation by CBP/p300. We also establish that this is a general transcriptional regulatory mechanism that applies to ~7% of expressed protein-coding genes in primary human airway epithelial cells. We observed that a homeostatic mechanism maintains promoter, but not enhancer, H3K18/27ac in response to extensive inhibition of CBP/p300 acetyl transferase activity by the highly specific small molecule inhibitor A-485. Further, our results suggest a function for BRD4 association at enhancers in regulating paused Pol2 release at nearby promoters. Taken together, our results uncover the processes regulating transcriptional elongation by promoter region histone H3 acetylation and homeostatic maintenance of promoter, but not enhancer, H3K18/27ac in response to inhibition of CBP/p300 acetyl transferase activity.

How a single genome can give rise to distinct cell types remains a fundamental question in biology. Mammals are able to specify and maintain hundreds of cell fates by selectively activating unique subsets of their genome. This is achieved, in part, by enhancers—genetic elements that can increase transcription of both nearby and distal genes. Enhancers can be identified by their unique chromatin signature, including transcription factor binding and the enrichment of specific histone post-translational modifications, histone variants, and chromatin-associated cofactors. How each of these chromatin features contributes to enhancer function remains an area of intense study. In this review, we provide an overview of enhancer-associated chromatin states, and the proteins and enzymes involved in their establishment. We discuss recent insights into the effects of the enhancer chromatin state on ongoing transcription versus their role in the establishment of new transcription programmes, such as those that occur developmentally. Finally, we highlight the role of enhancer chromatin in new conceptual advances in gene regulation such as condensate formation.

Background: Regulatory elements may be involved in the mechanisms by which 52 loci influence myocardial mass, reflected by abnormal amplitude and duration of the QRS complex on the ECG. Functional annotation thus far did not take into account how these elements are affected in disease context. Methods: We generated maps of regulatory elements on hypertrophic cardiomyopathy patients (ChIP-seq N=14 and RNA-seq N=11) and nondiseased hearts (ChIP-seq N=4 and RNA-seq N=11). We tested enrichment of QRS-associated loci on elements differentially acetylated and directly regulating differentially expressed genes between hypertrophic cardiomyopathy patients and controls. We further performed functional annotation on QRS-associated loci using these maps of differentially active regulatory elements. Results: Regions differentially affected in disease showed a stronger enrichment ( P =8.6×10 −5 ) for QRS-associated variants than those not showing differential activity ( P =0.01). Promoters of genes differentially regulated between hypertrophic cardiomyopathy patients and controls showed more enrichment ( P =0.001) than differentially acetylated enhancers ( P =0.8) and super-enhancers ( P =0.025). We also identified 74 potential causal variants overlapping these differential regulatory elements. Eighteen of the genes mapped confirmed previous findings, now also pinpointing the potentially affected regulatory elements and candidate causal variants. Fourteen new genes were also mapped. Conclusions: Our results suggest differentially active regulatory elements between hypertrophic cardiomyopathy patients and controls can offer more insights into the mechanisms of QRS-associated loci than elements not affected by disease.