Global Reprogramming of Apoptosis-Related Genes during Brain Development

To enable long-term survival, mammalian adult neurons exhibit unique apoptosis competence. Questions remain as to whether and how neurons globally reprogram the expression of apoptotic genes during development. We systematically examined the in vivo expression of 1923 apoptosis-related genes and ass...

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Autores principales:	Wei Jiang, Liang Chen, Sika Zheng
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	epigenome <i>Bax</i> <i>Bak1</i> <i>Casp3</i> <i>Casp7</i> <i>Casp6</i> Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9a8be59d6b634a73a80ac75470ad5715
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spelling	oai:doaj.org-article:9a8be59d6b634a73a80ac75470ad57152021-11-25T17:08:42ZGlobal Reprogramming of Apoptosis-Related Genes during Brain Development10.3390/cells101129012073-4409https://doaj.org/article/9a8be59d6b634a73a80ac75470ad57152021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2901https://doaj.org/toc/2073-4409To enable long-term survival, mammalian adult neurons exhibit unique apoptosis competence. Questions remain as to whether and how neurons globally reprogram the expression of apoptotic genes during development. We systematically examined the in vivo expression of 1923 apoptosis-related genes and associated histone modifications at eight developmental ages of mouse brains. Most apoptotic genes displayed consistent temporal patterns across the forebrain, midbrain, and hindbrain, suggesting ubiquitous robust developmental reprogramming. Although both anti- and pro-apoptotic genes can be up- or downregulated, half the regulatory events in the classical apoptosis pathway are downregulation of pro-apoptotic genes. Reduced expression in initiator caspases, apoptosome, and pro-apoptotic Bcl-2 family members restrains effector caspase activation and attenuates neuronal apoptosis. The developmental downregulation of apoptotic genes is attributed to decreasing histone-3-lysine-4-trimethylation (H3K4me3) signals at promoters, where histone-3-lysine-27-trimethylation (H3K27me3) rarely changes. By contrast, repressive H3K27me3 marks are lost in the upregulated gene groups, for which developmental H3K4me3 changes are not predictive. Hence, developing brains remove epigenetic H3K4me3 and H3K27me3 marks on different apoptotic gene groups, contributing to their downregulation and upregulation, respectively. As such, neurons drastically alter global apoptotic gene expression during development to transform apoptosis controls. Research into neuronal cell death should consider maturation stages as a biological variable.Wei JiangLiang ChenSika ZhengMDPI AGarticleepigenome<i>Bax</i><i>Bak1</i><i>Casp3</i><i>Casp7</i><i>Casp6</i>Biology (General)QH301-705.5ENCells, Vol 10, Iss 2901, p 2901 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epigenome <i>Bax</i> <i>Bak1</i> <i>Casp3</i> <i>Casp7</i> <i>Casp6</i> Biology (General) QH301-705.5
spellingShingle	epigenome <i>Bax</i> <i>Bak1</i> <i>Casp3</i> <i>Casp7</i> <i>Casp6</i> Biology (General) QH301-705.5 Wei Jiang Liang Chen Sika Zheng Global Reprogramming of Apoptosis-Related Genes during Brain Development
description	To enable long-term survival, mammalian adult neurons exhibit unique apoptosis competence. Questions remain as to whether and how neurons globally reprogram the expression of apoptotic genes during development. We systematically examined the in vivo expression of 1923 apoptosis-related genes and associated histone modifications at eight developmental ages of mouse brains. Most apoptotic genes displayed consistent temporal patterns across the forebrain, midbrain, and hindbrain, suggesting ubiquitous robust developmental reprogramming. Although both anti- and pro-apoptotic genes can be up- or downregulated, half the regulatory events in the classical apoptosis pathway are downregulation of pro-apoptotic genes. Reduced expression in initiator caspases, apoptosome, and pro-apoptotic Bcl-2 family members restrains effector caspase activation and attenuates neuronal apoptosis. The developmental downregulation of apoptotic genes is attributed to decreasing histone-3-lysine-4-trimethylation (H3K4me3) signals at promoters, where histone-3-lysine-27-trimethylation (H3K27me3) rarely changes. By contrast, repressive H3K27me3 marks are lost in the upregulated gene groups, for which developmental H3K4me3 changes are not predictive. Hence, developing brains remove epigenetic H3K4me3 and H3K27me3 marks on different apoptotic gene groups, contributing to their downregulation and upregulation, respectively. As such, neurons drastically alter global apoptotic gene expression during development to transform apoptosis controls. Research into neuronal cell death should consider maturation stages as a biological variable.
format	article
author	Wei Jiang Liang Chen Sika Zheng
author_facet	Wei Jiang Liang Chen Sika Zheng
author_sort	Wei Jiang
title	Global Reprogramming of Apoptosis-Related Genes during Brain Development
title_short	Global Reprogramming of Apoptosis-Related Genes during Brain Development
title_full	Global Reprogramming of Apoptosis-Related Genes during Brain Development
title_fullStr	Global Reprogramming of Apoptosis-Related Genes during Brain Development
title_full_unstemmed	Global Reprogramming of Apoptosis-Related Genes during Brain Development
title_sort	global reprogramming of apoptosis-related genes during brain development
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9a8be59d6b634a73a80ac75470ad5715
work_keys_str_mv	AT weijiang globalreprogrammingofapoptosisrelatedgenesduringbraindevelopment AT liangchen globalreprogrammingofapoptosisrelatedgenesduringbraindevelopment AT sikazheng globalreprogrammingofapoptosisrelatedgenesduringbraindevelopment
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Global Reprogramming of Apoptosis-Related Genes during Brain Development

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