title: Ubiquitously expressed genes participate in cell-specific functions via alternative promoter usage.
abstract: How do different cell types acquire their specific identities and functions is a fundamental question of biology. Previously significant efforts have been devoted to search for cell-type-specifically expressed genes, especially transcription factors, yet how do ubiquitously expressed genes participate in the formation or maintenance of cell-type-specific features remains largely unknown. Here, we have identified 110 mouse embryonic stem cell (mESC) specifically expressed transcripts with cell-stage-specific alternative transcription start sites (SATS isoforms) from 104 ubiquitously expressed genes, majority of which have active epigenetic modification- or stem cell-related functions. These SATS isoforms are specifically expressed in mESCs, and tend to be transcriptionally regulated by key pluripotency factors through direct promoter binding. Knocking down the SATS isoforms of Nmnat2 or Usp7 leads to differentiation-related phenotype in mESCs. These results demonstrate that cell-type-specific transcription factors are capable to produce cell-type-specific transcripts with alternative transcription start sites from ubiquitously expressed genes, which confer ubiquitously expressed genes novel functions involved in the establishment or maintenance of cell-type-specific features.
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences, Beijing, China Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development Institute of Genetics and Developmental Biology Chinese Academy of Sciences, Beijing, China.
authors.forename: Guihai
authors.initials: G
authors.lastname: Feng
authors.affiliation: Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development Institute of Genetics and Developmental Biology Chinese Academy of Sciences, Beijing, China.
authors.forename: Man
authors.initials: M
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Baolong
authors.initials: B
authors.lastname: Xia
authors.affiliation: Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development Institute of Genetics and Developmental Biology Chinese Academy of Sciences, Beijing, China.
authors.forename: Guan-Zheng
authors.initials: GZ
authors.lastname: Luo
authors.affiliation: Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development Institute of Genetics and Developmental Biology Chinese Academy of Sciences, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development Institute of Genetics and Developmental Biology Chinese Academy of Sciences, Beijing, China.
authors.forename: Dongfang
authors.initials: D
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences, Beijing, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences, Beijing, China qzhou@ioz.ac.cn xjwang@genetics.ac.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Genetic Network Biology, Collaborative Innovation Center of Genetics and Development Institute of Genetics and Developmental Biology Chinese Academy of Sciences, Beijing, China qzhou@ioz.ac.cn xjwang@genetics.ac.cn.
authors.forename: Xiu-Jie
authors.identifier: 0000-0001-7865-0204
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D004251:DNA Transposable Elements; D053595:Embryonic Stem Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000378:metabolism; D024363:Transcription Initiation Site; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D014157:Transcription Factors; D009612:Nicotinamide-Nucleotide Adenylyltransferase; C579543:Nmnat2 protein, mouse; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases; C579190:Usp7 protein, mouse
keywords: embryonic stem cell; pluripotency factors; stage‐specific alternative transcription start sites; ubiquitously expressed genes