Expression of class I histone deacetylases during chick and mouse development

Abstract

Histone deacetylases (HDACs) are a family of enzymes which regulate the acetylation state of nucleosomal histones, as well as non-histone proteins. By altering local chromatin architecture, HDACs play important roles in shaping cell differentiation and morphogenesis. Expression of class I HDACs during early chick development has so far not been analyzed. Here, we report the expression profile of chick class I HDACs from the onset of gastrulation (HH2) to day 4 of development and compare it to relevant stages during mouse development. Visualized by in situ hybridization to whole mount embryos and tissue sections, we found tissue-specific overlapping temporal and spatial expression domains for all four class I HDACs in chick and mouse, although species-specific differences could be identified. All class I HDACs in both species are highly expressed in the developing brain. In particular, HDAC1 is expressed at sites of anterior and posterior neural tube closure most obvious in the hot spot-like expression of HDAC1 in HH12 chicken embryos. A significant species-specific spatio-temporal expression pattern was observed for HDAC8. Whereas HDAC8 is exclusively found in fore-and midbrain regions during early mouse embryogenesis, the chick ortholog shows an expanded expression pattern, suggesting a more diversified role of HDAC8 in the chick system. Our results present a basis for further functional analysis of class I HDACs in chick development. KEY WORDS: histone deacetylase, chromatin, development, chick, mouseTranscriptional regulation in eukaryotes occurs within a chromatin setting and is strongly influenced by the posttranslational modification (PTM) of histones, the building blocks of chromatin. PTMs, such as methylation, phosphorylation and acetylation largely influence the readout of gene expression and represent an interface for binding factors and chromatin modifying enzymes (Strahl and Allis, 2000). A "histone code" has been suggested for the combination of distinct histone modifications that dramatically escalates the functional plasticity of the genome beyond the onedimensional nature of the primary DNA sequence (Jenuwein and Allis, 2001). Reversible histone acetylation is a dynamic process controlled by the antagonistic actions of two large families of enzymes -the histone acetyltransferases (HATs) and the histone deacetylases (HDACs). HDACs remove acetyl moieties from histone tails, resulting in chromatin condensation and an overall reduction in transcriptional potential, while HAT activity results in local opening of chromatin thereby setting the stage for transcripInt. J. Dev. Biol. 54: 1527-1537 (2010) doi: 10.1387/ijdb.092971cm tion. By controlling dynamic acetylation patterns at specific chromatin regions, HATs and HDACs also modulate the affinity of acetyl-histone binding factors. The balance between the actions of these enzymes serves as a key regulatory mechanism for gene expression and plays important roles in the programming of multicellular development. Furthermore, it has been demons...

Histone deacetylase 1 expression is inversely correlated with age in the short-lived fish Nothobranchius furzeri

“…For example, class I HDACs are highly expressed in the developing mouse and chicken brain (Murko et al 2010) and in the zebrafish central nervous system (Yamaguchi et al 2005). The adult mouse brain represents an interesting deviation from well-described HDAC1 and HDAC2 expression patterns in various proliferating cell types.…”

HDAC8-Mediated Epigenetic Reprogramming Plays a Key Role in Resistance to Anthrax Lethal Toxin–Induced Pyroptosis in Macrophages

“…HDAC8 is constitutively active and widely expressed (33,39,40). To date, HDAC8 was shown to be involved in adenoviral E1A-12 protein-mediated gene suppression of the histocompatibility complex I genes (41) and transcriptional repression by the inversion-16 fusion gene products in acute myeloid leukemia cells (42).…”

“…Although substrates for HDAC8 are not well defined, acetylated histones are main targets of HDAC8 (33). Thus, we examined the levels of histone acetylation in wild-type and TIR cells using Western blots.…”

Inhibition of Interleukin 1β (IL-1β) Expression by Anthrax Lethal Toxin (LeTx) Is Reversed by Histone Deacetylase 8 (HDAC8) Inhibition in Murine Macrophages

“…HDAC8 is a member of the class I HDACs that are mainly localized in the nucleus and deacetylate core histones (40). However, unlike others, HDAC8 is localized both in the cytoplasm and nucleus and was shown to deacetylate the core histones H2A/H2B, H3, and H4 in vitro (38 -40) but not yet in vivo (41,56,65,66). Failure in detecting histones as in vivo substrates of HDAC8 could be due to highly complex post-translational modifications at the N terminus of histones and limitations in sensitivity and specificity of the experimental approaches.…”