O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability
Cellular identity in multicellular organisms is maintained by characteristic transcriptional networks, nutrient consumption, energy production and metabolite utilization. Integrating these cell-specific programs are epigenetic modifiers, whose activity is often dependent on nutrients and their metab...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.605263/full |
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| author | Daniel Konzman Lara K. Abramowitz Agata Steenackers Mana Mohan Mukherjee Hyun-Jin Na John A. Hanover |
| author_facet | Daniel Konzman Lara K. Abramowitz Agata Steenackers Mana Mohan Mukherjee Hyun-Jin Na John A. Hanover |
| author_sort | Daniel Konzman |
| collection | DOAJ |
| description | Cellular identity in multicellular organisms is maintained by characteristic transcriptional networks, nutrient consumption, energy production and metabolite utilization. Integrating these cell-specific programs are epigenetic modifiers, whose activity is often dependent on nutrients and their metabolites to function as substrates and co-factors. Emerging data has highlighted the role of the nutrient-sensing enzyme O-GlcNAc transferase (OGT) as an epigenetic modifier essential in coordinating cellular transcriptional programs and metabolic homeostasis. OGT utilizes the end-product of the hexosamine biosynthetic pathway to modify proteins with O-linked β-D-N-acetylglucosamine (O-GlcNAc). The levels of the modification are held in check by the O-GlcNAcase (OGA). Studies from model organisms and human disease underscore the conserved function these two enzymes of O-GlcNAc cycling play in transcriptional regulation, cellular plasticity and mitochondrial reprogramming. Here, we review these findings and present an integrated view of how O-GlcNAc cycling may contribute to cellular memory and transgenerational inheritance of responses to parental stress. We focus on a rare human genetic disorder where mutant forms of OGT are inherited or acquired de novo. Ongoing analysis of this disorder, OGT- X-linked intellectual disability (OGT-XLID), provides a window into how epigenetic factors linked to O-GlcNAc cycling may influence neurodevelopment. |
| first_indexed | 2024-12-11T17:40:10Z |
| format | Article |
| id | doaj.art-6b5c99780d7a4f2894c3a26cde53d240 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-11T17:40:10Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-6b5c99780d7a4f2894c3a26cde53d2402022-12-22T00:56:33ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-11-011110.3389/fgene.2020.605263605263O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual DisabilityDaniel KonzmanLara K. AbramowitzAgata SteenackersMana Mohan MukherjeeHyun-Jin NaJohn A. HanoverCellular identity in multicellular organisms is maintained by characteristic transcriptional networks, nutrient consumption, energy production and metabolite utilization. Integrating these cell-specific programs are epigenetic modifiers, whose activity is often dependent on nutrients and their metabolites to function as substrates and co-factors. Emerging data has highlighted the role of the nutrient-sensing enzyme O-GlcNAc transferase (OGT) as an epigenetic modifier essential in coordinating cellular transcriptional programs and metabolic homeostasis. OGT utilizes the end-product of the hexosamine biosynthetic pathway to modify proteins with O-linked β-D-N-acetylglucosamine (O-GlcNAc). The levels of the modification are held in check by the O-GlcNAcase (OGA). Studies from model organisms and human disease underscore the conserved function these two enzymes of O-GlcNAc cycling play in transcriptional regulation, cellular plasticity and mitochondrial reprogramming. Here, we review these findings and present an integrated view of how O-GlcNAc cycling may contribute to cellular memory and transgenerational inheritance of responses to parental stress. We focus on a rare human genetic disorder where mutant forms of OGT are inherited or acquired de novo. Ongoing analysis of this disorder, OGT- X-linked intellectual disability (OGT-XLID), provides a window into how epigenetic factors linked to O-GlcNAc cycling may influence neurodevelopment.https://www.frontiersin.org/articles/10.3389/fgene.2020.605263/fullO-linked β-D-N-acetylglucosamine (O-GlcNAc)X-linked intellectual disability (XLID)epigeneticshistone modificationDNA methylationnutrient-sensing |
| spellingShingle | Daniel Konzman Lara K. Abramowitz Agata Steenackers Mana Mohan Mukherjee Hyun-Jin Na John A. Hanover O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability Frontiers in Genetics O-linked β-D-N-acetylglucosamine (O-GlcNAc) X-linked intellectual disability (XLID) epigenetics histone modification DNA methylation nutrient-sensing |
| title | O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability |
| title_full | O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability |
| title_fullStr | O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability |
| title_full_unstemmed | O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability |
| title_short | O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability |
| title_sort | o glcnac regulator of signaling and epigenetics linked to x linked intellectual disability |
| topic | O-linked β-D-N-acetylglucosamine (O-GlcNAc) X-linked intellectual disability (XLID) epigenetics histone modification DNA methylation nutrient-sensing |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.605263/full |
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