Direct transcriptional regulation of Six6 is controlled by SoxB1 binding to a remote forebrain enhancer.

Developmental Biology
Bumwhee LeeYongsu Jeong

Abstract

Six6, a sine oculis homeobox protein, plays a crucial and conserved role in the development of the forebrain and eye. To understand how the expression of Six6 is regulated during embryogenesis, we screened ~250 kb of genomic DNA encompassing the Six6 locus for cis-regulatory elements capable of directing reporter gene expression to sites of Six6 transcription in transgenic mouse embryos. Here, we describe two novel enhancer elements, that are highly conserved in vertebrate species and whose activities recapitulate Six6 expression in the ventral forebrain and eye, respectively. Cross-species comparisons of the Six6 forebrain enhancer sequences revealed highly conserved binding sites matching the consensus for homeodomain and SoxB1 transcription factors. Deletion of either of the binding sites resulted in loss of the forebrain enhancer activity in the ventral forebrain. Moreover, our studies show that members of the SoxB1 family, including Sox2 and Sox3, are expressed in the overlapping region of the ventral forebrain with Six6 and can bind to the Six6 forebrain enhancer. Loss of function of SoxB1 genes in vivo further emphasizes their role in regulating Six6 forebrain enhancer activity. Thus, our data strongly suggest that SoxB1...Continue Reading

References

Apr 25, 1994·Nucleic Acids Research·V R HarleyP N Goodfellow
Feb 11, 1993·Nucleic Acids Research·E M WrightP Koopman
Jun 1, 1997·Current Opinion in Genetics & Development·L H Pevny, R Lovell-Badge
Sep 2, 1998·Proceedings of the National Academy of Sciences of the United States of America·J ToyO H Sundin
Jun 25, 1999·Mechanisms of Development·J Toy, O H Sundin
Aug 24, 1999·Cell·M E ZuberW A Harris
Mar 24, 2000·Trends in Genetics : TIG·Y KamachiH Kondoh
Sep 26, 2002·Developmental Biology·Peter Carlsson, Margit Mahlapuu
Nov 13, 2002·American Journal of Human Genetics·Frédéric LaumonnierSylvain Briault
Apr 1, 2003·Molecular and Cellular Biology·Yoshimi TokuzawaShinya Yamanaka
Sep 2, 2003·Neuron·Victoria GrahamLarysa Pevny
Oct 1, 2003·Nature Neuroscience·Magdalena BylundJonas Muhr
Oct 18, 2003·Science·Marcelo A NobregaEdward M Rubin
Oct 31, 2003·Molecular and Cellular Biology·Jeffrey WeissJ Larry Jameson
Feb 26, 2004·Nature Genetics·Karine RizzotiRobin Lovell-Badge
Feb 22, 2005·Current Opinion in Neurobiology·Larysa Pevny, Marysia Placzek
May 3, 2006·Genes & Development·Olena V TaranovaLarysa H Pevny
Jul 13, 2006·American Journal of Medical Genetics. Part a·Leisha D NolenRobyn V Jamieson
Aug 26, 2006·The Journal of Clinical Investigation·Daniel KelbermanMehul T Dattani
Oct 9, 2007·Developmental Biology·Michelle L BrinkmeierSally A Camper
Feb 21, 2008·The Journal of Clinical Endocrinology and Metabolism·Daniel KelbermanMehul T Dattani
Oct 7, 2008·Nature Genetics·Yongsu JeongDouglas J Epstein
Jul 28, 2009·Cellular and Molecular Life Sciences : CMLS·Satoru MiyagiAkihiko Okuda
Oct 27, 2009·The International Journal of Biochemistry & Cell Biology·Pascal Bernard, Vincent R Harley
Jan 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rachel LarderPamela L Mellon
Nov 17, 2011·Genes & Development·Maria BergslandJonas Muhr

❮ Previous
Next ❯

Citations

Dec 21, 2013·American Journal of Medical Genetics. Part a·María Luisa Martínez-FríasSalvador Martínez
Jan 15, 2015·Journal of Molecular Endocrinology·Karine Rizzoti
Nov 30, 2019·Frontiers in Endocrinology·Katia MarinielloLeonardo Guasti
May 11, 2018·PloS One·Stefan NagelHans G Drexler
May 13, 2017·Scientific Reports·Andrew J Veale, Michael A Russello
Dec 17, 2020·Frontiers in Neuroanatomy·Carmen Diaz, Luis Puelles

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.