Histone deacetylases 1 and 2 are expressed at distinct stages of neuro‐glial development

MacDonald, Jessica L.; Roskams, A. Jane

doi:10.1002/dvdy.21626

Cited by 153 publications

(155 citation statements)

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“…HDAC1 and HDAC2 expression during brain development has been extensively studied and show relatively contrasting expression patterns throughout the central nervous system. HDAC1 is highly expressed in glia, whereas HDAC2 shows high expression in mature neurons, however, both are expressed in neuronal stem cells/progenitors during embryonic development (13). HDAC1 loxP/loxP ; GFAP-Cre and HDAC2 loxP/loxP ; GFAP-Cre mice were born at normal Mendelian ratios and showed normal brain histoarchitecture, behavior, motor skills, and lifespan (supporting information (SI) Fig.…”

Section: Resultsmentioning

confidence: 98%

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Montgomery¹,

Hsieh²,

Barbosa³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

277

254

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The molecular mechanism by which neural progenitor cells commit to a specified lineage of the central nervous system remains unknown. We show that HDAC1 and HDAC2 redundantly control neuronal development and are required for neuronal specification. Mice lacking HDAC1 or HDAC2 in neuronal precursors show no overt histoarchitectural phenotypes, whereas deletion of both HDAC1 and HDAC2 in developing neurons results in severe hippocampal abnormalities, absence of cerebellar foliation, disorganization of cortical neurons, and lethality by postnatal day 7. These abnormalities in brain formation can be attributed to a failure of neuronal precursors to differentiate into mature neurons and to excessive cell death. These results reveal redundant and essential roles for HDAC1 and HDAC2 in the progression of neuronal precursors to mature neurons in vivo.cerebellum ͉ hippocampus ͉ neurogenesis ͉ neuronal precursors H istone acetyltransferases (HATs) and histone deacetylases (HDACs) provide the enzymatic basis for transcriptional activation and repression, respectively, through alterations of the chromatin landscape (1). Transcription factors recruit HDACs, either individually, or in repressive complexes to deacetylate lysine residues on histone tails, resulting in chromatin condensation and repression of gene expression (2). There are 4 classes of HDACs that coordinate proper gene regulation for numerous cellular processes: class I (HDAC1, -2, -3, and -8), class II (HDAC4, -5, -6, -7, -9, and -10), sirtuin class III, and class IV (HDAC11) (3). Although much has been learned through in vitro and inhibitor studies, little is known about the biological function of these individual enzymes in vivo (4). We have shown that the class I HDACs, HDAC1 and HDAC2, redundantly regulate cardiac growth and morphogenesis (5), however, the functions of HDAC1 and HDAC2 in other tissues remain unknown.HDAC inhibitors have shown significant potential for therapeutic use in a variety of disorders, including those of the central nervous system (CNS), such as neurodegenerative disease, motor neuron disease, and a number of other neurological disease states (6). Furthermore, it has been shown that HDAC inhibitors induce differentiation of both embryonic and adult cortical neuronal progenitor cells to neurons specifically (7-9). The wide expression pattern of a number of HDACs in the developing brain suggests specific roles for individual HDACs in neuronal development (10), however, the broad inhibition of classical HDAC inhibitors has precluded the analysis of individual HDACs pharmacologically. Additionally, the early lethality associated with global deletion of class I HDACs in knockout mice has compounded the difficulties in analyzing the functions of these enzymes during specific stages of neurogenesis in vivo (5, 11).To further investigate the specific roles of HDAC1 and HDAC2 in neuronal development, we generated conditional deletions of HDAC1 and HDAC2 in the central nervous system. Here, we show both HDAC1 and HDAC2 are required for multip...

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Section: Resultsmentioning

confidence: 98%

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Montgomery¹,

Hsieh²,

Barbosa³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

277

254

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“…To better understand the molecular mechanisms through which E 2 might increase histone H3 acetylation, we measured protein and mRNA expression of the HDAC enzymes 1 and 2 (HDAC1 and HDAC2) in dorsal hippocampus after IH E 2 infusion. Both HDACs are expressed in adult mouse hippocampus, where HDAC1 is expressed in glia and neural progenitor cells, and HDAC2 is expressed in neurons and neural progenitors (16). HDAC1 regulates cell proliferation and differentiation and is neuroprotective in mouse forebrain (17).…”

Section: Resultsmentioning

confidence: 99%

Epigenetic alterations regulate estradiol-induced enhancement of memory consolidation

Zhao¹,

Liu²,

Frick

2010

Proc. Natl. Acad. Sci. U.S.A.

191

325

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The involvement of epigenetic alterations in mediating effects of estrogens on memory is unknown. The present study determined whether histone acetylation and DNA methylation are critical for the potent estrogen 17β-estradiol (E 2 ) to enhance object recognition memory. We show that dorsal hippocampal E 2 infusion increases acetylation of dorsal hippocampal histone H3, but not H4-an effect blocked by dorsal hippocampal inhibition of ERK activation. Further, intrahippocampal inhibition of ERK activation or DNA methyltransferase (DNMT) activity blocked the memory-enhancing effects of E 2 . Consistent with these effects, E 2 decreased levels of HDAC2 protein and increased DNMT expression in the dorsal hippocampus. These findings provide evidence that the beneficial effects of E 2 on memory consolidation are associated with epigenetic alterations, and suggest these can be triggered by dorsal hippocampal ERK signaling.T he specific molecular mechanisms underlying the mnemonic effects of estrogens remain largely unknown. We recently showed that activation of the extracellular signal-regulated kinase/ mitogen-activated protein kinase (ERK/MAPK) signaling cascade in the dorsal hippocampus is necessary for the potent estrogen 17β-estradiol (E 2 ) to enhance novel object recognition in young female mice (1). In this study, i.p. injection of E 2 immediately after object recognition training significantly enhanced long-term memory and increased p42 ERK phosphorylation in the dorsal hippocampus; both effects were blocked by inhibiting MAPK kinase (MEK), the exclusive upstream activator of ERK (1).Activated ERK can promote the expression of genes associated with learning and memory, in part, by activating transcription factors such as CREB (2, 3). ERK may also increase gene expression by regulating epigenetic mechanisms necessary for memory formation, such as histone acetylation and DNA methylation; recent findings suggest that ERK activation influences both processes (4-7). Thus, these mechanisms may also play a role in estrogenic modulation of memory. DNA is wound around a core of eight histone proteins, two each of histones H2A, H2B, H3, and H4. Acetylation of lysine residues on histone tails relaxes the bond between histones and DNA, allowing transcriptional access. Histone acetylation is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs) (8). Genetic disruption of HAT activity impairs hippocampal memory, and these deficits are rescued by HDAC inhibitors (9). HDAC inhibitors such as trichostatin A (TSA) prevent deacetylation of histones H3 and H4, and enhance induction of hippocampal long-term potentiation (LTP), long-term contextual fear conditioning (CFC), and novel object recognition (4, 10-12). Acetylation of hippocampal histone H3, but not H4, is increased following ERK activation or CFC (4, 5), and ERK activation is necessary for other protein kinases (e.g., protein kinase C, PKC) to increase hippocampal H3 acetylation (4). Collectively, these data suggest that histone acetylation regul...

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“…In the mouse system MacDonald and Roskams reported that both HDAC1 and HDAC2 are expressed in neural progenitor and stem cells (MacDonald and Roskams, 2008). Strikingly, upon lineage specification into either glial cells or neuroblasts and post-mitotic neurons, HDAC1 and HDAC2 are found to be mutually exclusive expressed.…”

Section: Hdac1 and Hdac2 In Heart Developmentmentioning

confidence: 99%

Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation

Brunmeir¹,

Lagger²,

Seiser³

2009

Int. J. Dev. Biol.

154

147

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During development from the fertilized egg to a multicellular organism, cell fate decisions have to be taken and cell lineage or tissue-specific gene expression patterns are created and maintained. These alterations in gene expression occur in the context of chromatin structure and are controlled by chromatin modifying enzymes. Gene disruption studies in different genetic systems have shown an essential role of various histone deacetylases (HDACs) during early development and cellular differentiation. In this review, we focus on the functions of the class I enzymes HDAC1 and HDAC2 during development in different organisms and summarise the current knowledge about their involvement in neurogenesis, myogenesis, haematopoiesis and epithelial cell differentiation. KEY WORDS: HDAC1, HDAC2, chromatin, differentiation, development Histone deacetylasesPosttranslational modifications of histones cause changes in the accessibility of DNA, thereby regulating many important cellular processes including transcription. Acetylation of core histones leads to a change in the net positive charge of histone tails and local opening of chromatin structure, a feature of transcriptionally active genes. On the other hand, deacetylated histone tails interact more closely with DNA and lead to a repressive state. Histone deacetylases (HDACs) catalyse the removal of acetyl groups from histone tails and are therefore considered as transcriptional corepressors. In addition to histones, HDACs also deacetylate non-histone proteins, such as the cytoskeletal protein tubulin (Hubbert et al., 2002) or transcription factors including p53 (Luo et al., 2000), E2F1 (MartinezBalbas et al., 2000) and YY1 (Yao et al., 2001). In fact, phylogenetic analysis suggests that the enzymatic activity was initially directed against non-histone proteins in a common ancestor devoid of histones (Gregoretti et al., 2004). In mammals, 18 deacetylases have been identified so far. These enzymes have been divided into 4 classes based on sequence similarity: Classic HDACs comprise class I (Saccharomyces cerevisiae Rpd3-like), class II (Saccharomyces cerevisiae Hda1-like) and class IV (HDAC11-like) enzymes. Class III consists of NAD-dependent, functionally unrelated Sir2-like deacetylases Int. J. Dev. Biol. 53: 275-289 (2009) Abbreviations used in this paper: HAT, histone acetyltransferase; HDA, HDAC, histone deacetylase; HDI, HDAC inhibitor; NuRD, nucleosome remodelling and deacetylase complex; Rpd3, reduced potassium dependency 3.named "sirtuins". Class I, II and IV HDACs are members of an ancient enzyme family, highly conserved throughout eukaryotic and prokaryotic evolution and are found in animals, plants, fungi, archaebacteria and eubacteria (Gregoretti et al., 2004). Class I histone deacetylasesPhylogenetic analysis revealed that class I genes in animals can be grouped into HDAC1/HDAC2, HDAC3 and HDAC8-like genes. Members of each subclass have been identified in protostomia (Oger et al., 2008) and deuterostomia. Species analysed so far carry orthologs (...

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Histone deacetylases 1 and 2 are expressed at distinct stages of neuro‐glial development

Cited by 153 publications

References 55 publications

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development

Epigenetic alterations regulate estradiol-induced enhancement of memory consolidation

Histone deacetylase HDAC1/HDAC2-controlled embryonic development and cell differentiation

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