Histone deacetylases 1 and 2 are required for brain development

Abstract

Epigenetic modifications of histones have been implicated in the regulation of cell specific expression of genes required for neuronal development. The best studied post-translational (epigenetic) modification of histones is the process of reversible acetylation. Two types of enzymeshistone acetyltransferases (HATs) and histone deacetylases (HDACs) establish and maintain specific patterns of histone acetylation in balance, thereby contributing to both transcriptional activation and repression of specific sets of genes. Histone deacetylases catalyze the removal of acetyl groups from selected lysine residues in the conserved tails of core histone proteins and are considered as transcriptional corepressors. A significant amount of data implicates HDACs in diverse biological processes, including tissue specific developmental program by silencing specific growth-inhibitory genes. In line with this, gene disruption studies have shown that the class I deacetylases, HDAC1 and HDAC2 play an essential role in nervous system development. In the present review, we briefly highlight current insights supporting the function of histone deacetylases in rodent brain development and discuss present knowledge referring to their role in neurogenesis, taking into consideration results obtained in culture systems and in in vivo studies.

Targeting Oxidative Stress Reduction and Inhibition of HDAC1, MECP2, and NF-kB Pathways in Rats With Experimentally Induced Hyperglycemia by Administration of Thymus marshallianus Willd. Extracts

“…Histone deacetylases, (HDACs), a family of four classes enzymes, divided into zinc (class I: HDACs 1, 2, 3 and 8; class II: HDACs 4, 5, 6, 7, 9 and 10; class IV: HDAC 11) and nicotinamide adenine dinucleotide -dependent groups (class III HDACs: sirtuins), play a major role in the normal cellular brain activities by regulating, gene expression, survival or proliferation of the cells (Reddy et al, 2018;Gatla et al, 2019). Class I HDACs, expressed in various mammalian cells and tissues, have been intensively studied as histone modifiers and transcriptional repressors (Jaworska et al, 2015). Moreover, the importance of both HDAC1 and 2 in the development of CNS, as hdac 1 mutation induced neuron and glia failure cell formation in the hindbrain, loss of segmental organization of postmitotic neurons and glia cells and deficit in the branching of motor neurons in zebrafish (Pillai et al, 2004;MacDonald and Roskams, 2008).…”

Tumorigenesis as a process of gradual loss of original cell identity and gain of properties of neural precursor/progenitor cells

“…Because each of these enzymes regulates different chromatin modifications and non-histone proteins, it is very complex to analyze the exact molecular mechanisms underlying the differentiation effect. However, there are reports supporting their roles in regulating neurogenesis or neural development [ 62 – 64 ]. Regardless of the precise molecular mechanisms, the important information is that, similar to differentiation of a particular type of tissue or organ from their respective precursor/progenitor cells during embryonic development, neuron-like differentiation of distinct cancer cell lines provides the convincing evidence that cancer cells possess the potential for neuronal differentiation, a key property of neural precursor/progenitor cells.…”

Epigenetic regulators Rbbp4 and Hdac1 are overexpressed in a zebrafish model of RB1 embryonal brain tumor, and are required for neural progenitor survival and proliferation

“…Studies in zebrafish show that hdac1 is necessary for central and peripheral nervous system development ( Henion et al, 1996 ; Ignatius et al, 2013 ), and is required for cell cycle exit and differentiation of neural precursors in the retina ( Stadler et al, 2005 ; Yamaguchi et al, 2005 ). The role of HDAC1 in promoting proliferation versus differentiation could depend on the type and location of the neural cell population examined ( Jaworska et al, 2015 ). Examining the contribution of HDAC1 and RBBP4 to maintaining the progenitor-like state of RB1 brain tumors would shed light on the mechanism of chromatin remodeling in epigenetic control of tumor suppression.…”