An Evolutionarily Conserved Mesodermal Enhancer in Vertebrate Zic3

Overview

Journal Sci Rep

Specialty Science

Date 2018 Oct 10

PMID 30297839

Citations 3

Authors

Yuri S Odaka

Takahide Tohmonda

Atsushi Toyoda

Jun Aruga

Affiliations

Soon will be listed here.

Abstract

Zic3 encodes a zinc finger protein essential for the development of meso-ectodermal tissues. In mammals, Zic3 has important roles in the development of neural tube, axial skeletons, left-right body axis, and in maintaining pluripotency of ES cells. Here we characterized cis-regulatory elements required for Zic3 expression. Enhancer activities of human-chicken-conserved noncoding sequences around Zic1 and Zic3 were screened using chick whole-embryo electroporation. We identified enhancers for meso-ectodermal tissues. Among them, a mesodermal enhancer (Zic3-ME) in distant 3' flanking showed robust enhancement of reporter gene expression in the mesodermal tissue of chicken and mouse embryos, and was required for mesodermal Zic3 expression in mice. Zic3-ME minimal core region is included in the DNase hypersensitive region of ES cells, mesoderm, and neural progenitors, and was bound by T (Brachyury), Eomes, Lef1, Nanog, Oct4, and Zic2. Zic3-ME is derived from an ancestral sequence shared with a sequence encoding a mitochondrial enzyme. These results indicate that Zic3-ME is an integrated cis-regulatory element essential for the proper expression of Zic3 in vertebrates, serving as a hub for a gene regulatory network including Zic3.

Citing Articles

SMPD3 expression is spatially regulated in the developing embryo by SOXE factors.

Piacentino M, Fasse A, Camacho-Avila A, Grabylnikov I, Bronner M Dev Biol. 2023; 506:31-41.

PMID: 38052296 PMC: 10872304. DOI: 10.1016/j.ydbio.2023.11.011.

An intronic enhancer of Cebpa regulates adipocyte differentiation and adipose tissue development via long-range loop formation.

Li X, Zeng S, Chen L, Zhang Y, Li X, Zhang B Cell Prolif. 2023; 57(3):e13552.

PMID: 37905345 PMC: 10905358. DOI: 10.1111/cpr.13552.

Exploring high-resolution chromatin interaction changes and functional enhancers of myogenic marker genes during myogenic differentiation.

Long K, Li X, Su D, Zeng S, Li H, Zhang Y J Biol Chem. 2022; 298(8):102149.

PMID: 35787372 PMC: 9352921. DOI: 10.1016/j.jbc.2022.102149.

References

Aruga J, Millen K . ZIC1 Function in Normal Cerebellar Development and Human Developmental Pathology. Adv Exp Med Biol. 2018; 1046:249-268. DOI: 10.1007/978-981-10-7311-3_13. View

Warner S, Hutson M, Oh S, Gerlach-Bank L, Lomax M, Barald K . Expression of ZIC genes in the development of the chick inner ear and nervous system. Dev Dyn. 2003; 226(4):702-12. DOI: 10.1002/dvdy.10262. View

Hamburger V, HAMILTON H . A series of normal stages in the development of the chick embryo. J Morphol. 2014; 88(1):49-92. View

Inoue T, Ota M, Mikoshiba K, Aruga J . Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo. Dev Biol. 2007; 306(2):669-84. DOI: 10.1016/j.ydbio.2007.04.003. View

Zuin J, Dixon J, van der Reijden M, Ye Z, Kolovos P, Brouwer R . Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells. Proc Natl Acad Sci U S A. 2013; 111(3):996-1001. PMC: 3903193. DOI: 10.1073/pnas.1317788111. View

Mizugishi K, Aruga J, Nakata K, Mikoshiba K . Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins. J Biol Chem. 2000; 276(3):2180-8. DOI: 10.1074/jbc.M004430200. View

Fujimi T, Hatayama M, Aruga J . Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway. Dev Biol. 2011; 361(2):220-31. DOI: 10.1016/j.ydbio.2011.10.026. View

Nyholm M, Wu S, Dorsky R, Grinblat Y . The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum. Development. 2007; 134(4):735-46. DOI: 10.1242/dev.02756. View

McMahon A, Merzdorf C . Expression of the zic1, zic2, zic3, and zic4 genes in early chick embryos. BMC Res Notes. 2010; 3:167. PMC: 2908108. DOI: 10.1186/1756-0500-3-167. View

10.

Yevshin I, Sharipov R, Valeev T, Kel A, Kolpakov F . GTRD: a database of transcription factor binding sites identified by ChIP-seq experiments. Nucleic Acids Res. 2016; 45(D1):D61-D67. PMC: 5210645. DOI: 10.1093/nar/gkw951. View

11.

Galan-Caridad J, Harel S, Arenzana T, Hou Z, Doetsch F, Mirny L . Zfx controls the self-renewal of embryonic and hematopoietic stem cells. Cell. 2007; 129(2):345-57. PMC: 1899089. DOI: 10.1016/j.cell.2007.03.014. View

12.

Mayor R, Guerrero N, Young R, Gomez-Skarmeta J, Cuellar C . A novel function for the Xslug gene: control of dorsal mesendoderm development by repressing BMP-4. Mech Dev. 2000; 97(1-2):47-56. DOI: 10.1016/s0925-4773(00)00412-3. View

13.

Mei S, Qin Q, Wu Q, Sun H, Zheng R, Zang C . Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic Acids Res. 2016; 45(D1):D658-D662. PMC: 5210658. DOI: 10.1093/nar/gkw983. View

14.

Uchikawa M, Nishimura N, Iwafuchi-Doi M, Kondoh H . Enhancer Analyses Using Chicken Embryo Electroporation. Methods Mol Biol. 2017; 1650:191-202. DOI: 10.1007/978-1-4939-7216-6_12. View

15.

Ahmed J, Ali R, Warr N, Wilson H, Bellchambers H, Barratt K . A murine Zic3 transcript with a premature termination codon evades nonsense-mediated decay during axis formation. Dis Model Mech. 2013; 6(3):755-67. PMC: 3634658. DOI: 10.1242/dmm.011668. View

16.

Garnett A, Square T, Medeiros D . BMP, Wnt and FGF signals are integrated through evolutionarily conserved enhancers to achieve robust expression of Pax3 and Zic genes at the zebrafish neural plate border. Development. 2012; 139(22):4220-31. PMC: 4074300. DOI: 10.1242/dev.081497. View

17.

Aruga J . The role of Zic genes in neural development. Mol Cell Neurosci. 2004; 26(2):205-21. DOI: 10.1016/j.mcn.2004.01.004. View

18.

Hatayama M, Aruga J . Role of Zic Family Proteins in Transcriptional Regulation and Chromatin Remodeling. Adv Exp Med Biol. 2018; 1046:353-380. DOI: 10.1007/978-981-10-7311-3_18. View

19.

Lim L, Loh Y, Zhang W, Li Y, Chen X, Wang Y . Zic3 is required for maintenance of pluripotency in embryonic stem cells. Mol Biol Cell. 2007; 18(4):1348-58. PMC: 1838990. DOI: 10.1091/mbc.e06-07-0624. View

20.

Maeda R, Mood K, Jones T, Aruga J, Buchberg A, Daar I . Xmeis1, a protooncogene involved in specifying neural crest cell fate in Xenopus embryos. Oncogene. 2001; 20(11):1329-42. DOI: 10.1038/sj.onc.1204250. View