Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition

doi:10.1016/J.STEM.2013.05.006

Home
/
Papers
/
Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition

Journal Article•DOI•

Tet1 Regulates Adult Hippocampal Neurogenesis and Cognition

Runrui Zhang¹, Qingyan Cui¹, Kiyohito Murai², Yen Ching Lim³, Zachary D. Smith⁴, Zachary D. Smith⁵, Shengnan Jin³, Peng Ye², Luis Rosa², Yew Kok Lee³, Hai-Ping Wu¹, Wei Liu¹, Zhi-Mei Xu¹, Lu Yang⁶, Yu-Qiang Ding⁷, Yu-Qiang Ding⁸, Fuchou Tang⁶, Alexander Meissner⁴, Alexander Meissner⁵, Chunming Ding³, Yanhong Shi², Guoliang Xu¹ - Show less +18 more•Institutions (8)

Laboratory of Molecular Biology¹, City of Hope National Medical Center², Agency for Science, Technology and Research³, Harvard University⁴, Broad Institute⁵, Peking University⁶, Tongji University⁷, Chinese Ministry of Education⁸

01 Aug 2013-Cell Stem Cell (Cell Stem Cell)-Vol. 13, Iss: 2, pp 237-245

TL;DR: It is demonstrated that Tet1 plays an important role in regulating neural progenitor cell proliferation in adult mouse brain, and that it is positively involved in the epigenetic regulation of neural progensitor cells proliferation in the adult brain.

read less

About: This article is published in Cell Stem Cell.The article was published on 2013-08-01 and is currently open access. It has received 320 citations till now. The article focuses on the topics: Neurogenesis & Progenitor cell.

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

TET-mediated active DNA demethylation: mechanism, function and beyond

[...]

Xiaoji Wu¹, Yi Zhang•Institutions (1)

Howard Hughes Medical Institute¹

30 May 2017-Nature Reviews Genetics

TL;DR: Recent advances in biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation and many regulatory mechanisms of this process have been identified.

...read moreread less

Abstract: A key mode of regulating DNA methylation is through active demethylation driven by TET-mediated oxidation of 5-methylcytosine (5mC). This Review discusses our latest understanding of the mechanisms and regulation of active DNA demethylation, and the roles of active demethylation (and the oxidized 5mC intermediates) in gene regulation, genome stability, development and disease.

...read moreread less

1,012 citations

Journal Article•DOI•

Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions

[...]

Hao Wu, Yi Zhang

16 Jan 2014-Cell

TL;DR: The mechanism and function of DNA demethylation in mammalian genomes is discussed, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes.

...read moreread less

886 citations

Cites background from "Tet1 Regulates Adult Hippocampal Ne..."

...…/ mice have no detectable defects in embryonic development, a recent study demonstrates that TET1 may promote adult hippocampal neurogenesis by regulating neural progenitor proliferation and Tet1-deficiency may cause defects in spatial learning as well as short-term memory (Zhang et al., 2013)....
[...]
...Analysis of DNA methylation by RRBS and gene expression in Tet1-deficient NPCs isolated from adult dentate gyrus (DG) of hippocampus identified a cohort of genes that become promoter hypermethylated and downregulated in the absence of TET1(Zhang et al., 2013)....
[...]
...While Tet1 / mice have no detectable defects in embryonic development, a recent study demonstrates that TET1 may promote adult hippocampal neurogenesis by regulating neural progenitor proliferation and Tet1-deficiency may cause defects in spatial learning as well as short-term memory (Zhang et al., 2013)....
[...]

Journal Article•DOI•

Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

[...]

Allison M. Bond¹, Guo Li Ming, Hongjun Song¹•Institutions (1)

Johns Hopkins University School of Medicine¹

01 Oct 2015-Cell Stem Cell

TL;DR: Recent progress is reviewed and questions related to adult mammalian neural stem cells that also apply to other somatic stem cells are focused on.

...read moreread less

585 citations

Cites background from "Tet1 Regulates Adult Hippocampal Ne..."

...Active DNA demethylation, mediated by the TET-GADD45 pathway (Guo et al., 2011), regulates SGZ NSC proliferation both cell autonomously (Zhang et al., 2013) and non-cell autonomously via modulation of growth factor expression in mature granule neurons (Ma et al., 2009)....
[...]
..., 2011), regulates SGZ NSC proliferation both cell autonomously (Zhang et al., 2013) and non-cell autonomously via modulation of growth factor expression in mature granule neu-...
[...]

Journal Article•DOI•

Chromatin modifiers and remodellers: regulators of cellular differentiation

[...]

Taiping Chen¹, Sharon Y.R. Dent•Institutions (1)

University of Texas MD Anderson Cancer Center¹

01 Feb 2014-Nature Reviews Genetics

TL;DR: Genome-wide profiling of pluripotent cells and differentiated cells suggests global chromatin remodelling during differentiation, which results in a progressive transition from a fairly open chromatin configuration to a more compact state, rather than merely stabilizing the gene expression changes that are driven by developmental transcription factors.

...read moreread less

Abstract: This Review describes the diverse roles for histone-modifying and chromatin-remodelling enzymes in mammalian differentiation. These enzymes are involved in both maintaining pluripotency and specifying cell lineage commitment. Recent progress includes their functional characterization in mouse modelsin vivoand a new appreciation of their multifaceted molecular functions. Cellular differentiation is, by definition, epigenetic. Genome-wide profiling of pluripotent cells and differentiated cells suggests global chromatin remodelling during differentiation, which results in a progressive transition from a fairly open chromatin configuration to a more compact state. Genetic studies in mouse models show major roles for a variety of histone modifiers and chromatin remodellers in key developmental transitions, such as the segregation of embryonic and extra-embryonic lineages in blastocyst stage embryos, the formation of the three germ layers during gastrulation and the differentiation of adult stem cells. Furthermore, rather than merely stabilizing the gene expression changes that are driven by developmental transcription factors, there is emerging evidence that chromatin regulators have multifaceted roles in cell fate decisions.

...read moreread less

564 citations

Journal Article•DOI•

5-Hydroxymethylcytosine is a predominantly stable DNA modification.

[...]

Martin Bachman¹, Santiago Uribe-Lewis¹, Xiaoping Yang¹, Michael J.A. Williams¹, Adele Murrell¹, Shankar Balasubramanian¹ - Show less +2 more•Institutions (1)

University of Cambridge¹

01 Dec 2014-Nature Chemistry

TL;DR: Using stable isotope labelling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry, it is shown that the majority of hmC is a stable modification, as opposed to a transient intermediate, which has important implications for understanding the states of chemically modified DNA bases in health and disease.

...read moreread less

Abstract: 5-Hydroxymethylcytosine (hmC) is an oxidation product of 5-methylcytosine which is present in the deoxyribonucleic acid (DNA) of most mammalian cells. Reduction of hmC levels in DNA is a hallmark of cancers. Elucidating the dynamics of this oxidation reaction and the lifetime of hmC in DNA is fundamental to understanding hmC function. Using stable isotope labelling of cytosine derivatives in the DNA of mammalian cells and ultrasensitive tandem liquid-chromatography mass spectrometry, we show that the majority of hmC is a stable modification, as opposed to a transient intermediate. In contrast with DNA methylation, which occurs immediately during replication, hmC forms slowly during the first 30 hours following DNA synthesis. Isotopic labelling of DNA in mouse tissues confirmed the stability of hmC in vivo and demonstrated a relationship between global levels of hmC and cell proliferation. These insights have important implications for understanding the states of chemically modified DNA bases in health and disease.

...read moreread less

444 citations

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1

[...]

Mamta Tahiliani¹, Kian Peng Koh¹, Yinghua Shen², William A. Pastor¹, Hozefa S. Bandukwala¹, Yevgeny Brudno², Suneet Agarwal¹, Lakshminarayan M. Iyer³, David R. Liu², L. Aravind³, Anjana Rao¹ - Show less +7 more•Institutions (3)

Harvard University¹, Howard Hughes Medical Institute², National Institutes of Health³

15 May 2009-Science

TL;DR: It is shown here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro.

...read moreread less

Abstract: DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse embryonic stem cells, and hmC levels decrease upon RNA interference–mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.

...read moreread less

5,155 citations

"Tet1 Regulates Adult Hippocampal Ne..." refers background in this paper

...Thismodification is derived from the hydroxylation of 5mCand the conversion is catalyzed by the Tet family of dioxygenases in an Fe (II)- and a-ketoglutaratedependent manner (Tahiliani et al., 2009; Tan and Shi, 2012)....
[...]

Journal Article•DOI•

Morris water maze: procedures for assessing spatial and related forms of learning and memory

[...]

Charles V. Vorhees¹, Michael T. Williams¹•Institutions (1)

University of Cincinnati Academic Health Center¹

01 Jan 2006-Nature Protocols

TL;DR: The Morris water maze has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function and trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol.

...read moreread less

Abstract: The Morris water maze (MWM) is a test of spatial learning for rodents that relies on distal cues to navigate from start locations around the perimeter of an open swimming arena to locate a submerged escape platform. Spatial learning is assessed across repeated trials and reference memory is determined by preference for the platform area when the platform is absent. Reversal and shift trials enhance the detection of spatial impairments. Trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol. Search-to-platform area determines the degree of reliance on spatial versus non-spatial strategies. Cued trials determine whether performance factors that are unrelated to place learning are present. Escape from water is relatively immune from activity or body mass differences, making it ideal for many experimental models. The MWM has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function. We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days.

...read moreread less

3,331 citations

"Tet1 Regulates Adult Hippocampal Ne..." refers background or methods in this paper

...The Morris water maze was conducted as described elsewhere (Vorhees and Williams, 2006)....
[...]
...Morris Water Maze The Morris water maze was conducted as described elsewhere (Vorhees and Williams, 2006)....
[...]
...Recent epigenomic studies have revealed in mature neurons an enrichment of 5hmC in gene bodies that may act as a stable active mark recognizable by MeCP2 (Hahn et al., 2013; Mellén et al., 2012; Song et al., 2011; Szulwach et al., 2011; Vorhees and Williams, 2006)....
[...]
...Recent epigenomic studies have revealed in mature neurons an enrichment of 5hmC in gene bodies that may act as a stable active mark recognizable by MeCP2 (Hahn et al., 2013; Mellén et al., 2012; Song et al., 2011; Szulwach et al., 2011; Vorhees and Williams, 2006)....
[...]

Journal Article•DOI•

Mechanisms and functional implications of adult neurogenesis.

[...]

Chunmei Zhao¹, Wei Deng¹, Fred H. Gage¹•Institutions (1)

Salk Institute for Biological Studies¹

22 Feb 2008-Cell

TL;DR: The factors that regulate proliferation and fate determination of adult neural stem cells are discussed and the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease is addressed.

...read moreread less

2,911 citations

"Tet1 Regulates Adult Hippocampal Ne..." refers background in this paper

...The potential significance of this remodeling process has been illustrated in memory, depression, and neurodegenerative disorders (Zhao et al., 2008)....
[...]
...The maintenance and differentiation of neural progenitors in these two regions are regulated by many molecular players and signaling pathways, including niche signals, neurotransmitters, growth factors, transcriptional factors, and epigenetic regulators (Mu et al., 2010; Zhao et al., 2008)....
[...]

Journal Article•DOI•

The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain

[...]

Skirmantas Kriaucionis¹, Nathaniel Heintz¹•Institutions (1)

Howard Hughes Medical Institute¹

15 May 2009-Science

TL;DR: It is shown that, as well as 5mC in mammalian genomes, there are also significant amounts of 5-hydroxymethylcytosine (5hmC) in DNA of Purkinje neurons, which have large nuclei with apparently very little heterochromatin.

...read moreread less

Abstract: Despite the importance of epigenetic regulation in neurological disorders, little is known about neuronal chromatin. Cerebellar Purkinje neurons have large and euchromatic nuclei, whereas granule cell nuclei are small and have a more typical heterochromatin distribution. While comparing the abundance of 5-methylcytosine in Purkinje and granule cell nuclei, we detected the presence of an unusual DNA nucleotide. Using thin-layer chromatography, high-pressure liquid chromatography, and mass spectrometry, we identified the nucleotide as 5-hydroxymethyl-2′-deoxycytidine (hmdC). hmdC constitutes 0.6% of total nucleotides in Purkinje cells, 0.2% in granule cells, and is not present in cancer cell lines. hmdC is a constituent of nuclear DNA that is highly abundant in the brain, suggesting a role in epigenetic control of neuronal function.

...read moreread less

2,558 citations

Journal Article•DOI•

Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA

[...]

Yu-Fei He¹, Bin-Zhong Li¹, Zheng Li¹, Peng Liu¹, Yang Wang¹, Qingyu Tang¹, Jianping Ding¹, Yingying Jia¹, Zhangcheng Chen¹, Lin Li¹, Yan Sun², Xiuxue Li², Qing Dai³, Chun-Xiao Song³, Kangling Zhang⁴, Chuan He³, Guoliang Xu¹ - Show less +13 more•Institutions (4)

Laboratory of Molecular Biology¹, Chinese Academy of Sciences², University of Chicago³, Loma Linda University⁴

02 Sep 2011-Science

TL;DR: It is demonstrated that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells, suggesting that oxidation of 5m C by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.

...read moreread less

Abstract: The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.

...read moreread less

2,408 citations

"Tet1 Regulates Adult Hippocampal Ne..." refers background in this paper

...Since Tet family proteins can catalyze hydroxylation of 5mC, their role in promoting active DNA demethylation has prompted intensive research (Branco et al., 2012; Cortellino et al., 2011; Guo et al., 2011b; He et al., 2011;Williams et al., 2011)....
[...]