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Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation

Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 (KMT2B) are essential for oogen...

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Autores principales: Hanna, Courtney W, Huang, Jiahao, Belton, Christian, Reinhardt, Susanne, Dahl, Andreas, Andrews, Simon, Stewart, A Francis, Kranz, Andrea, Kelsey, Gavin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887468/
https://www.ncbi.nlm.nih.gov/pubmed/35137160
http://dx.doi.org/10.1093/nar/gkac051
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author Hanna, Courtney W
Huang, Jiahao
Belton, Christian
Reinhardt, Susanne
Dahl, Andreas
Andrews, Simon
Stewart, A Francis
Kranz, Andrea
Kelsey, Gavin
author_facet Hanna, Courtney W
Huang, Jiahao
Belton, Christian
Reinhardt, Susanne
Dahl, Andreas
Andrews, Simon
Stewart, A Francis
Kranz, Andrea
Kelsey, Gavin
author_sort Hanna, Courtney W
collection PubMed
description Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 (KMT2B) are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) oocytes using ultra-low input ChIP-seq, with comparisons to DNA methylation and gene expression analyses. H3K4me3 was redistributed in Setd1b cKO oocytes showing losses at active gene promoters associated with downregulated gene expression. Remarkably, many regions also gained H3K4me3, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich, which are hallmarks of MLL2 targets. Consequently, loss of SETD1B disrupts the balance between MLL2 and de novo DNA methyltransferases in determining the epigenetic landscape during oogenesis. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression and MLL2 to CpG content.
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spelling pubmed-88874682022-03-02 Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation Hanna, Courtney W Huang, Jiahao Belton, Christian Reinhardt, Susanne Dahl, Andreas Andrews, Simon Stewart, A Francis Kranz, Andrea Kelsey, Gavin Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 (KMT2B) are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) oocytes using ultra-low input ChIP-seq, with comparisons to DNA methylation and gene expression analyses. H3K4me3 was redistributed in Setd1b cKO oocytes showing losses at active gene promoters associated with downregulated gene expression. Remarkably, many regions also gained H3K4me3, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich, which are hallmarks of MLL2 targets. Consequently, loss of SETD1B disrupts the balance between MLL2 and de novo DNA methyltransferases in determining the epigenetic landscape during oogenesis. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to gene expression and MLL2 to CpG content. Oxford University Press 2022-02-07 /pmc/articles/PMC8887468/ /pubmed/35137160 http://dx.doi.org/10.1093/nar/gkac051 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Hanna, Courtney W
Huang, Jiahao
Belton, Christian
Reinhardt, Susanne
Dahl, Andreas
Andrews, Simon
Stewart, A Francis
Kranz, Andrea
Kelsey, Gavin
Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation
title Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation
title_full Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation
title_fullStr Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation
title_full_unstemmed Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation
title_short Loss of histone methyltransferase SETD1B in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation
title_sort loss of histone methyltransferase setd1b in oogenesis results in the redistribution of genomic histone 3 lysine 4 trimethylation
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8887468/
https://www.ncbi.nlm.nih.gov/pubmed/35137160
http://dx.doi.org/10.1093/nar/gkac051
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