title: Bat Accelerated Regions Identify a Bat Forelimb Specific Enhancer in the HoxD Locus.
abstract: The molecular events leading to the development of the bat wing remain largely unknown, and are thought to be caused, in part, by changes in gene expression during limb development. These expression changes could be instigated by variations in gene regulatory enhancers. Here, we used a comparative genomics approach to identify regions that evolved rapidly in the bat ancestor, but are highly conserved in other vertebrates. We discovered 166 bat accelerated regions (BARs) that overlap H3K27ac and p300 ChIP-seq peaks in developing mouse limbs. Using a mouse enhancer assay, we show that five Myotis lucifugus BARs drive gene expression in the developing mouse limb, with the majority showing differential enhancer activity compared to the mouse orthologous BAR sequences. These include BAR116, which is located telomeric to the HoxD cluster and had robust forelimb expression for the M. lucifugus sequence and no activity for the mouse sequence at embryonic day 12.5. Developing limb expression analysis of Hoxd10-Hoxd13 in Miniopterus natalensis bats showed a high-forelimb weak-hindlimb expression for Hoxd10-Hoxd11, similar to the expression trend observed for M. lucifugus BAR116 in mice, suggesting that it could be involved in the regulation of the bat HoxD complex. Combined, our results highlight novel regulatory regions that could be instrumental for the morphological differences leading to the development of the bat wing.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America.|Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Betty M
authors.initials: BM
authors.lastname: Booker
authors.affiliation: Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.|Gladstone Institutes, San Francisco, California, United States of America.
authors.forename: Tara
authors.initials: T
authors.lastname: Friedrich
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Mandy K
authors.initials: MK
authors.lastname: Mason
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America.|Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Julia E
authors.initials: JE
authors.lastname: VanderMeer
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America.|Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.|Key Laboratory of Advanced Control and Optimization for Chemical Processes of the Ministry of Education, East China University of Science and Technology, Shanghai, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America.|Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Eckalbar
authors.affiliation: Division of Developmental Biology, MRC-National Institute for Medical Research, Mill Hill, London, United Kingdom.|Randall Division of Cell and Molecular Biophysics, King's College London, Guys Campus, London, United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Logan
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South Africa.
authors.forename: Nicola
authors.initials: N
authors.lastname: Illing
authors.affiliation: Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.|Gladstone Institutes, San Francisco, California, United States of America.|Division of Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Pollard
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, California, United States of America.|Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
mesh_terms: D000818:Animals; D002685:Chiroptera / Q000235:genetics* / Q000254:growth & development; D004622:Embryo, Mammalian; D005552:Forelimb / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D023281:Genomics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D038081:Organogenesis / Q000235:genetics*; D016415:Sequence Alignment; D017421:Sequence Analysis; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014714:Vertebrates / Q000235:genetics* / Q000254:growth & development; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; C084118:Hoxd13 protein, mouse; D014157:Transcription Factors