HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

Abstract

Oocyte and preimplantation embryo development entail dynamic changes in chromatin structure and gene expression, which are regulated by a number of maternal and zygotic epigenetic factors. Histone deacetylases (HDACs), which tighten chromatin structure, repress transcription and gene expression by removing acetyl groups from histone or non-histone proteins. HDAC1 and HDAC2 are two highly homologous Class I HDACs and display compensatory or specific roles in different cell types or in response to different stimuli and signaling pathways. We summarize here the current knowledge about the functions of HDAC1 and HDAC2 in regulating histone modifications, transcription, DNA methylation, chromosome segregation, and cell cycle during oocyte and preimplantation embryo development. What emerges from these studies is that although HDAC1 and HDAC2 are highly homologous, HDAC2 is more critical than HDAC1 for oocyte development and reciprocally, HDAC1 is more critical than HDAC2 for preimplantation development. In eukaryotes, DNA is organized into a highly ordered nucleoprotein assembly called chromatin, whose fundamental unit is the nucleosome. The nucleosome consists of 146 bp of DNA wrapped around a histone core comprised of two molecules each of histones H2A, H2B, H3 and H4. Histone H1 is bound to linker DNA between nucleosomes. 1,2 Histones are subject to multiple post-translational modifications (PTMs), including acetylation, methylation, ubiquitylation, phosphorylation, and sumoylation. These PTMs determine open and closed chromatin conformations, which, in turn, regulate the differential access and recruitment of transcription factors and other regulatory chromatin-binding proteins to DNA. 3-5 Among these histone modifications, histone acetylation is the most well-studied modification, which occurs at the ε-amino groups of evolutionarily conserved lysine residues located at the N termini. Although all core histones are acetylated in vivo, modifications of histones H3 and H4 are more extensively characterized than those of H2A and H2B. Abbreviations: HDAC, histone deacetylase; HAT, histone acetyl transferase; PTM, post-translational modification; KDAC, lysine deacetylase; TSA, trichostatin A; NAD + , nicotinamide adenine dinucleotide; HAD, HDAC association domain ; GVBD, germinal vesicle breakdown; ChIP-seq, chromatin immunoprecipitation sequencing; TFIID, transcription factor II D; YY1, yin yang 1; Pol II CTD S2, serine 2 within the RNApolymerase II C-terminal domain; H3K4, lysine 4 of histone 3; H3K9, lysine 9 of histone 3; H4K16, lysine 16 of histone 4; SIRT, NAD-dependent deacetylase sirtuin; TBP2, TATA-binding protein 2; DNMT, DNA methyltransferases; RBAP46, retinoblastoma binding protein P46; RNAi, RNA interference; aa, amino acidic; BrUTP, 5-Bromouridine 5′-triphosphate; qRT-PCR, quantitative reverse transcription polymerase chain reaction;

Towards Functional Annotation of the Preimplantation Transcriptome: An RNAi Screen in Mammalian Embryos

“…In summary, GO term analysis offered no striking outliers in functional categories within our screen results and suggests that preimplantation development equally requires all aspects of cellular and molecular function for success. Supporting this notion, previous studies have found essential roles during preimplantation for genes within each of these functional categories (including DNA/RNA/protein binding4546, catalytic activity4748, various transporter activity495051). …”

An Essential Role of Maspin in Embryogenesis and Tumor Suppression

“…The biological activities of HDAC1 in embryogenesis appear to be distinct among HDAC isoforms and may differ from the HDAC1 functions in somatic cells of various differentiation lineages (45). Future studies are warranted to address whether the lack of maspin-mediated control of HDAC1 activity underlies the embryonic lethality of Maspin KO mice, and whether the cell type-specific expression of maspin and its inhibitory interaction with HDAC1 in embryogenesis are distinct from those in somatic tissues.…”

The histone codes for meiosis

“…H3K9ac and H3K14ac exist in these active transcription regions to create a microenvironment for recruiting transcriptional factors and RNA polymerase II at the GV stage in oocytes (Kim et al 2003, De La Fuente et al 2004, Gu et al 2010, Ding et al 2012. After meiosis resumes at the GVBD stage, these acetylations are removed by histone deacetylases (HDACs) to further condense the chromatin for meiotic division (Akiyama et al 2004, Ma & Schultz 2016.…”