气候变化领域集成服务门户(CCPortal): Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm

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DOI	10.1073/pnas.2025196118
	Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm
	Xu J.; Li J.; Zhang T.; Jiang H.; Ramakrishnan A.; Fritzsch B.; Shen L.; Xu P.-X.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Specification of Sox2+ proneurosensory progenitors within otic ectoderm is a prerequisite for the production of sensory cells and neurons for hearing. However, the underlying molecular mechanisms driving this lineage specification remain unknown. Here, we show that the Brg1-based SWI/SNF chromatin-remodeling complex interacts with the neurosensory-specific transcriptional regulators Eya1/Six1 to induce Sox2 expression and promote proneurosensory-lineage specification. Ablation of the ATPase-subunit Brg1 or both Eya1/Six1 results in loss of Sox2 expression and lack of neurosensory identity, leading to abnormal apoptosis within the otic ectoderm. Brg1 binds to two of three distal 3′ Sox2 enhancers occupied by Six1, and Brg1-binding to these regions depends on Eya1-Six1 activity. We demonstrate that the activity of these Sox2 enhancers in otic neurosensory cells specifically depends on binding to Six1. Furthermore, genome-wide and transcriptome profiling indicate that Brg1 may suppress apoptotic factor Map3k5 to inhibit apoptosis. Together, our findings reveal an essential role for Brg1, its downstream pathways, and their interactions with Six1/Eya1 in promoting proneurosensory fate induction in the otic ectoderm and subsequent neuronal lineage commitment and survival of otic cells. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Otic neurosensory lineage \| chromatin remodelers \| transcription factors \| Sox2 enhancers \| regulation of otic Sox2 expression
语种	英语
scopus关键词	apoptosis signal regulating kinase 1; BRG1 protein; SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily B member 1; transcription factor Six1; transcription factor Sox2; animal cell; apoptosis; Article; C57BL 6 mouse; cell survival; chromatin; controlled study; ectoderm; embryo; enhancer region; female; gene expression; genome-wide association study; mouse; nerve cell; nonhuman; priority journal; progenitor cell line; protein binding; protein expression; protein interaction; transcriptomics
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180138
作者单位	Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Neurosciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Biology, University of Iowa, Iowa City, IA 52242-1324, United States; Department of Otolaryngology, University of Iowa, Iowa City, IA 52242-1324, United States; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
推荐引用方式 GB/T 7714	Xu J.,Li J.,Zhang T.,et al. Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm[J],2021,118(12).
APA	Xu J..,Li J..,Zhang T..,Jiang H..,Ramakrishnan A..,...&Xu P.-X..(2021).Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Xu J.,et al."Chromatin remodelers and lineage-specific factors interact to target enhancers to establish proneurosensory fate within otic ectoderm".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).