MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons
DNA methylation-dependent gene silencing is initiated by DNA methyltransferases (DNMTs) and mediated by methyl-binding domain proteins (MBDs), which recruit histone deacetylases (HDACs) to silence DNA, a process that is essential for normal development. Here, we show that the MBD proteins MBD2 and M...
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| Veröffentlicht in: | Molecular and cellular neuroscience 2010-05, Vol.44 (1), p.55-67 |
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| creator | MacDonald, Jessica L. Verster, Adrian Berndt, Anthony Roskams, A. Jane |
| description | DNA methylation-dependent gene silencing is initiated by DNA methyltransferases (DNMTs) and mediated by methyl-binding domain proteins (MBDs), which recruit histone deacetylases (HDACs) to silence DNA, a process that is essential for normal development. Here, we show that the MBD proteins MBD2 and MeCP2 regulate distinct transitional stages of olfactory receptor neuron (ORN) differentiation
in vivo.
Mbd2 null progenitors display enhanced proliferation, recapitulated by HDAC inhibition, and
Mbd2 null ORNs have a decreased lifespan.
Mecp2 null ORNs, on the other hand, temporarily stall at the stage of terminal differentiation, retaining expression of the immature neuronal protein GAP43 after initiating expression of mature neuronal genes. The
Gap43 promoter is highly methylated in the mature, but not embryonic olfactory epithelium (OE), suggesting that
Gap43 may be regulated by DNA methylation during ORN differentiation. Thus, MBD2 and MeCP2 may mediate distinct, sequential transitions of ORN differentiation—an epigenetic mechanism that may be relevant to developmental regulation throughout the nervous system. |
| doi_str_mv | 10.1016/j.mcn.2010.02.003 |
| format | Article |
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in vivo.
Mbd2 null progenitors display enhanced proliferation, recapitulated by HDAC inhibition, and
Mbd2 null ORNs have a decreased lifespan.
Mecp2 null ORNs, on the other hand, temporarily stall at the stage of terminal differentiation, retaining expression of the immature neuronal protein GAP43 after initiating expression of mature neuronal genes. The
Gap43 promoter is highly methylated in the mature, but not embryonic olfactory epithelium (OE), suggesting that
Gap43 may be regulated by DNA methylation during ORN differentiation. Thus, MBD2 and MeCP2 may mediate distinct, sequential transitions of ORN differentiation—an epigenetic mechanism that may be relevant to developmental regulation throughout the nervous system.</description><identifier>ISSN: 1044-7431</identifier><identifier>EISSN: 1095-9327</identifier><identifier>DOI: 10.1016/j.mcn.2010.02.003</identifier><identifier>PMID: 20188178</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Differentiation - genetics ; Cell Proliferation ; DNA Methylation - physiology ; DNA-Binding Proteins - genetics ; Epigenesis, Genetic - genetics ; Epigenetics ; GAP-43 Protein - genetics ; GAP-43 Protein - metabolism ; Gene Expression Regulation, Developmental - genetics ; Gene Silencing - physiology ; Histone deacetylase ; Histone Deacetylases - genetics ; Histone Deacetylases - metabolism ; Male ; Methyl-CpG-Binding Protein 2 - genetics ; Mice ; Mice, Knockout ; Neural development ; Neurogenesis ; Neurogenesis - physiology ; Olfactory Mucosa - cytology ; Olfactory Mucosa - embryology ; Olfactory Mucosa - growth & development ; Olfactory Receptor Neurons - cytology ; Olfactory Receptor Neurons - metabolism ; Promoter Regions, Genetic - genetics</subject><ispartof>Molecular and cellular neuroscience, 2010-05, Vol.44 (1), p.55-67</ispartof><rights>2010 Elsevier Inc.</rights><rights>Copyright 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-4dbd2baf24d8ed4bfb353a3af6f481ef5aa3a131c4a6f4e82465d4dcc1abe29f3</citedby><cites>FETCH-LOGICAL-c450t-4dbd2baf24d8ed4bfb353a3af6f481ef5aa3a131c4a6f4e82465d4dcc1abe29f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mcn.2010.02.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20188178$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MacDonald, Jessica L.</creatorcontrib><creatorcontrib>Verster, Adrian</creatorcontrib><creatorcontrib>Berndt, Anthony</creatorcontrib><creatorcontrib>Roskams, A. Jane</creatorcontrib><title>MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons</title><title>Molecular and cellular neuroscience</title><addtitle>Mol Cell Neurosci</addtitle><description>DNA methylation-dependent gene silencing is initiated by DNA methyltransferases (DNMTs) and mediated by methyl-binding domain proteins (MBDs), which recruit histone deacetylases (HDACs) to silence DNA, a process that is essential for normal development. Here, we show that the MBD proteins MBD2 and MeCP2 regulate distinct transitional stages of olfactory receptor neuron (ORN) differentiation
in vivo.
Mbd2 null progenitors display enhanced proliferation, recapitulated by HDAC inhibition, and
Mbd2 null ORNs have a decreased lifespan.
Mecp2 null ORNs, on the other hand, temporarily stall at the stage of terminal differentiation, retaining expression of the immature neuronal protein GAP43 after initiating expression of mature neuronal genes. The
Gap43 promoter is highly methylated in the mature, but not embryonic olfactory epithelium (OE), suggesting that
Gap43 may be regulated by DNA methylation during ORN differentiation. Thus, MBD2 and MeCP2 may mediate distinct, sequential transitions of ORN differentiation—an epigenetic mechanism that may be relevant to developmental regulation throughout the nervous system.</description><subject>Animals</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Proliferation</subject><subject>DNA Methylation - physiology</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Epigenesis, Genetic - genetics</subject><subject>Epigenetics</subject><subject>GAP-43 Protein - genetics</subject><subject>GAP-43 Protein - metabolism</subject><subject>Gene Expression Regulation, Developmental - genetics</subject><subject>Gene Silencing - physiology</subject><subject>Histone deacetylase</subject><subject>Histone Deacetylases - genetics</subject><subject>Histone Deacetylases - metabolism</subject><subject>Male</subject><subject>Methyl-CpG-Binding Protein 2 - genetics</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neural development</subject><subject>Neurogenesis</subject><subject>Neurogenesis - physiology</subject><subject>Olfactory Mucosa - cytology</subject><subject>Olfactory Mucosa - embryology</subject><subject>Olfactory Mucosa - growth & development</subject><subject>Olfactory Receptor Neurons - cytology</subject><subject>Olfactory Receptor Neurons - metabolism</subject><subject>Promoter Regions, Genetic - genetics</subject><issn>1044-7431</issn><issn>1095-9327</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtPwzAQhC0EoqXwA7gg3zil-JU2EScoT6kIDnC2HHsNrlIn2A4S_x5XBY5w8q71zaw0g9AxJVNK6OxsNV1rP2Uk74RNCeE7aExJXRY1Z_PdzSxEMRecjtBBjCtCSMlqvo9GWVJVdF6NUf9wecWw8gY_wOKJ4QCvQ6sSYONicl4nnILy0SXX-Yidx-kNcEzqFYrYg3bW6YxaCwF8cmqD4c7irrVKpy58ZkMNfZ6whyFkj0O0Z1Ub4ej7naCXm-vnxV2xfLy9X1wsCy1KkgphGsMaZZkwFRjR2IaXXHFlZ1ZUFGyp8kI51ULlH6iYmJVGGK2paoDVlk_Q6da3D937ADHJtYsa2lZ56IYo52KWAyOE_k9yzuqqEiSTdEvq0MUYwMo-uLUKn5ISuWlErmRuRG4akYTJfCBrTr7dh2YN5lfxU0EGzrcA5DQ-HAQZtQOvwbicXZKmc3_YfwEq5Z3-</recordid><startdate>20100501</startdate><enddate>20100501</enddate><creator>MacDonald, Jessica L.</creator><creator>Verster, Adrian</creator><creator>Berndt, Anthony</creator><creator>Roskams, A. 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Jane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-4dbd2baf24d8ed4bfb353a3af6f481ef5aa3a131c4a6f4e82465d4dcc1abe29f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Proliferation</topic><topic>DNA Methylation - physiology</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Epigenesis, Genetic - genetics</topic><topic>Epigenetics</topic><topic>GAP-43 Protein - genetics</topic><topic>GAP-43 Protein - metabolism</topic><topic>Gene Expression Regulation, Developmental - genetics</topic><topic>Gene Silencing - physiology</topic><topic>Histone deacetylase</topic><topic>Histone Deacetylases - genetics</topic><topic>Histone Deacetylases - metabolism</topic><topic>Male</topic><topic>Methyl-CpG-Binding Protein 2 - genetics</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neural development</topic><topic>Neurogenesis</topic><topic>Neurogenesis - physiology</topic><topic>Olfactory Mucosa - cytology</topic><topic>Olfactory Mucosa - embryology</topic><topic>Olfactory Mucosa - growth & development</topic><topic>Olfactory Receptor Neurons - cytology</topic><topic>Olfactory Receptor Neurons - metabolism</topic><topic>Promoter Regions, Genetic - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MacDonald, Jessica L.</creatorcontrib><creatorcontrib>Verster, Adrian</creatorcontrib><creatorcontrib>Berndt, Anthony</creatorcontrib><creatorcontrib>Roskams, A. 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Jane</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons</atitle><jtitle>Molecular and cellular neuroscience</jtitle><addtitle>Mol Cell Neurosci</addtitle><date>2010-05-01</date><risdate>2010</risdate><volume>44</volume><issue>1</issue><spage>55</spage><epage>67</epage><pages>55-67</pages><issn>1044-7431</issn><eissn>1095-9327</eissn><abstract>DNA methylation-dependent gene silencing is initiated by DNA methyltransferases (DNMTs) and mediated by methyl-binding domain proteins (MBDs), which recruit histone deacetylases (HDACs) to silence DNA, a process that is essential for normal development. Here, we show that the MBD proteins MBD2 and MeCP2 regulate distinct transitional stages of olfactory receptor neuron (ORN) differentiation
in vivo.
Mbd2 null progenitors display enhanced proliferation, recapitulated by HDAC inhibition, and
Mbd2 null ORNs have a decreased lifespan.
Mecp2 null ORNs, on the other hand, temporarily stall at the stage of terminal differentiation, retaining expression of the immature neuronal protein GAP43 after initiating expression of mature neuronal genes. The
Gap43 promoter is highly methylated in the mature, but not embryonic olfactory epithelium (OE), suggesting that
Gap43 may be regulated by DNA methylation during ORN differentiation. Thus, MBD2 and MeCP2 may mediate distinct, sequential transitions of ORN differentiation—an epigenetic mechanism that may be relevant to developmental regulation throughout the nervous system.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20188178</pmid><doi>10.1016/j.mcn.2010.02.003</doi><tpages>13</tpages></addata></record> |
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| subjects | Animals Cell Differentiation - genetics Cell Proliferation DNA Methylation - physiology DNA-Binding Proteins - genetics Epigenesis, Genetic - genetics Epigenetics GAP-43 Protein - genetics GAP-43 Protein - metabolism Gene Expression Regulation, Developmental - genetics Gene Silencing - physiology Histone deacetylase Histone Deacetylases - genetics Histone Deacetylases - metabolism Male Methyl-CpG-Binding Protein 2 - genetics Mice Mice, Knockout Neural development Neurogenesis Neurogenesis - physiology Olfactory Mucosa - cytology Olfactory Mucosa - embryology Olfactory Mucosa - growth & development Olfactory Receptor Neurons - cytology Olfactory Receptor Neurons - metabolism Promoter Regions, Genetic - genetics |
| title | MBD2 and MeCP2 regulate distinct transitions in the stage-specific differentiation of olfactory receptor neurons |
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