Abstract
Organismal development and cell differentiation critically depend on chromatin state transitions. However, certain developmentally regulated genes lack histone 3 lysine 9 and 27 acetylation (H3K9ac and H3K27ac, respectively) and histone 3 lysine 4 (H3K4) methylation, histone modifications common to most active genes. Here we describe a chromatin state featuring unique histone 3 lysine 14 acetylation (H3K14ac) peaks in key tissue-specific genes in Drosophila and human cells. Replacing H3K14 in Drosophila demonstrates that H3K14 is essential for expression of genes devoid of canonical histone modifications in the embryonic gut and larval wing imaginal disc, causing lethality and defective wing patterning. We find that the SWI/SNF protein Brahma (Brm) recognizes H3K14ac, that brm acts in the same genetic pathway as H3K14R, and that chromatin accessibility at H3K14ac-unique genes is decreased in H3K14R mutants. Our results show that acetylation of a single lysine is essential at genes devoid of canonical histone marks and uncover an important requirement for H3K14 in tissue-specific gene regulation.
Highlights
Cellular differentiation and the response to environmental cues require altered gene expression and are associated with changes in chromatin state (Allis and Jenuwein, 2016; Atlasi and Stunnenberg, 2017)
A unique H3K14ac chromatin state The presence of H3K14ac in promoter regions is positively correlated with active gene expression in yeast and in mammalian cells (Karmodiya et al, 2012; Pokholok et al, 2005), suggesting an important biological role of H3K14ac in transcription activation
In stark contrast to these reports and to other histone modifications associated with active transcription, 30% of H3K14ac is found in exons in Drosophila
Summary
Cellular differentiation and the response to environmental cues require altered gene expression and are associated with changes in chromatin state (Allis and Jenuwein, 2016; Atlasi and Stunnenberg, 2017). Histone 3 lysine 27 trimethylation (H3K27me3) is found at Polycomb group (PcG)-repressed genes, whereas histone 3 lysine 4 trimethylation (H3K4me3) is often present at the promoters of transcriptionally active genes (Black et al, 2012). Some developmental genes lack these canonical histone marks but are transcriptionally active (Perez-Lluch et al, 2015). Whether these developmental genes bear another histone mark or whether they are completely devoid of histone modifications altogether is not known. We investigate the role of histone 3 lysine 14 acetylation (H3K14ac) in developmental gene expression and find that a group of tissue-specific genes that lack canonical histone marks are decorated uniquely with this histone modification
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