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Author

Michael Perry

Bio: Michael Perry is an academic researcher from New York University. The author has contributed to research in topics: Enhancer & Heliconius. The author has an hindex of 20, co-authored 51 publications receiving 1818 citations. Previous affiliations of Michael Perry include Ulster Hospital & University of California, Berkeley.
Topics: Enhancer, Heliconius, Facial trauma, Colias, Medicine


Papers
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Journal ArticleDOI
TL;DR: The results suggest that shadow enhancers represent a novel mechanism of canalization whereby complex developmental processes "bring about one definite end-result regardless of minor variations in conditions".

376 citations

Journal ArticleDOI
TL;DR: Evidence is presented that every gap gene contains multiple enhancers with overlapping activities to produce authentic patterns of gene expression, and different models for “enhancer synergy,” whereby two enhancersWith overlapping activities produce authentic Patterns of Gene expression are presented.
Abstract: Segmentation of the Drosophila embryo begins with the establishment of spatially restricted gap gene-expression patterns in response to broad gradients of maternal transcription factors, such as Bicoid. Numerous studies have documented the fidelity of these expression patterns, even when embryos are subjected to genetic or environmental stress, but the underlying mechanisms for this transcriptional precision are uncertain. Here we present evidence that every gap gene contains multiple enhancers with overlapping activities to produce authentic patterns of gene expression. For example, a recently identified hunchback (hb) enhancer (located 5-kb upstream of the classic enhancer) ensures repression at the anterior pole. The combination of intronic and 5′ knirps (kni) enhancers produces a faithful expression pattern, even though the intronic enhancer alone directs an abnormally broad expression pattern. We present different models for “enhancer synergy,” whereby two enhancers with overlapping activities produce authentic patterns of gene expression.

241 citations

Journal ArticleDOI
10 Aug 2017-Cell
TL;DR: It is demonstrated that the development of genetics in Harpegnathos establishes this ant species as a model organism to study the complexity of eusociality and striking functions of Orco in odorant perception, reproductive physiology, and social behavior plasticity are demonstrated.

170 citations

Journal ArticleDOI
12 Aug 2015-eLife
TL;DR: Quantitative modeling of enhancer–promoter interactions suggests that weakly active enhancers function additively while strong enhancers behave sub-additively due to competition with the target promoter.
Abstract: Metazoan genes are embedded in a rich milieu of regulatory information that often includes multiple enhancers possessing overlapping activities. In this study, we employ quantitative live imaging methods to assess the function of pairs of primary and shadow enhancers in the regulation of key patterning genes-knirps, hunchback, and snail-in developing Drosophila embryos. The knirps enhancers exhibit additive, sometimes even super-additive activities, consistent with classical gene fusion studies. In contrast, the hunchback enhancers function sub-additively in anterior regions containing saturating levels of the Bicoid activator, but function additively in regions where there are diminishing levels of the Bicoid gradient. Strikingly sub-additive behavior is also observed for snail, whereby removal of the proximal enhancer causes a significant increase in gene expression. Quantitative modeling of enhancer-promoter interactions suggests that weakly active enhancers function additively while strong enhancers behave sub-additively due to competition with the target promoter.

148 citations

Journal ArticleDOI
TL;DR: It is reported that a subset of developmental regulatory genes, enriched in critical RNA-processing factors, exhibits synchronous lengthening of their 3′ UTRs during embryogenesis, suggesting a previously unknown mode of posttranscriptional regulation that may contribute to the complexity of neurogenesis or neural function.
Abstract: The 3′ termini of eukaryotic mRNAs influence transcript stability, translation efficiency, and subcellular localization. Here we report that a subset of developmental regulatory genes, enriched in critical RNA-processing factors, exhibits synchronous lengthening of their 3′ UTRs during embryogenesis. The resulting UTRs are up to 20-fold longer than those found on typical Drosophila mRNAs. The large mRNAs emerge shortly after the onset of zygotic transcription, with several of these genes acquiring additional, phased UTR extensions later in embryogenesis. We show that these extended 3′ UTR sequences are selectively expressed in neural tissues and contain putative recognition motifs for the translational repressor, Pumilio, which also exhibits the 3′ lengthening phenomenon documented in this study. These findings suggest a previously unknown mode of posttranscriptional regulation that may contribute to the complexity of neurogenesis or neural function.

135 citations


Cited by
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Journal ArticleDOI
TL;DR: Current knowledge of transcription factor function from genomic and genetic studies is reviewed and how different strategies, including extensive cooperative regulation, progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development are discussed.
Abstract: Developmental progression is driven by specific spatiotemporal domains of gene expression, which give rise to stereotypically patterned embryos even in the presence of environmental and genetic variation. Views of how transcription factors regulate gene expression are changing owing to recent genome-wide studies of transcription factor binding and RNA expression. Such studies reveal patterns that, at first glance, seem to contrast with the robustness of the developmental processes they encode. Here, we review our current knowledge of transcription factor function from genomic and genetic studies and discuss how different strategies, including extensive cooperative regulation (both direct and indirect), progressive priming of regulatory elements, and the integration of activities from multiple enhancers, confer specificity and robustness to transcriptional regulation during development.

1,774 citations

Journal ArticleDOI
24 Apr 2015-Science
TL;DR: This report reports multiplexed error-robust FISH (MERFISH), a single-molecule imaging method that allows thousands of RNA species to be imaged in single cells by using combinatorial FISH labeling with encoding schemes capable of detecting and/or correcting errors.
Abstract: INTRODUCTION: The copy number and in- tracellular localization of RNA are important regulators of gene expression. Measurement of these properties at the transcriptome scale in single cells will give answers to many ques- tions related to gene expression and regulation. Single-molecule RNA imaging approaches, such as single-molecule fluorescence in situ hybrid- ization(smFISH), are powerful toolsforcount- ing and mappingRNA; however, the number of RNA species that can be simultaneously im- aged in individual cells has been limited. This makes it challenging to perform transcriptomic analysis of single cells in a spatially resolved manner. Here, we report multiplexed error- robust FISH (MERFISH), a single-molecule im- aging method that allows thousands of RNA species to be imaged in single cells by using combinatorial FISH labeling with encoding schemes capable of detecting and/or correct- ing errors. RATIONALE: We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently la- beled readout probes. Each RNA species is encodedwithaparticular combinationofread- out sequences. We used successive rounds of hybridization and imaging, each with a differ- ent readout probe, to identify the readout se- quences bound to each RNA and to decode the RNA. In principle, combinatorial labeling al- lows the number of detectable RNA species to

1,576 citations

01 Feb 2009
TL;DR: eMedicine创建于1996年,由近万名临床医师作为作者或编辑参与此临校医学知识库。
Abstract: eMedicine创建于1996年,由近万名临床医师作为作者或编辑参与此临床医学知识库的建设,其中编辑均是来自美国哈佛、耶鲁、斯坦福、芝加哥、德克萨斯、加州大学等各分校医学院的教授或副教授。

1,459 citations

Journal ArticleDOI
TL;DR: This work shows how cis-regulatory activity can diverge and how studies of cis-Regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.
Abstract: Cis-regulatory sequences, such as enhancers and promoters, control development and physiology by regulating gene expression. Mutations that affect the function of these sequences contribute to phenotypic diversity within and between species. With many case studies implicating divergent cis-regulatory activity in phenotypic evolution, researchers have recently begun to elucidate the genetic and molecular mechanisms that are responsible for cis-regulatory divergence. Approaches include detailed functional analysis of individual cis-regulatory elements and comparing mechanisms of gene regulation among species using the latest genomic tools. Despite the limited number of mechanistic studies published to date, this work shows how cis-regulatory activity can diverge and how studies of cis-regulatory divergence can address long-standing questions about the genetic mechanisms of phenotypic evolution.

919 citations

Journal ArticleDOI
01 Mar 2013-Science
TL;DR: STARR-seq identifies thousands of cell type–specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map, revealing the highly complex regulation of transcription.
Abstract: Genomic enhancers are important regulators of gene expression, but their identification is a challenge, and methods depend on indirect measures of activity. We developed a method termed STARR-seq to directly and quantitatively assess enhancer activity for millions of candidates from arbitrary sources of DNA, which enables screens across entire genomes. When applied to the Drosophila genome, STARR-seq identifies thousands of cell type–specific enhancers across a broad continuum of strengths, links differential gene expression to differences in enhancer activity, and creates a genome-wide quantitative enhancer map. This map reveals the highly complex regulation of transcription, with several independent enhancers for both developmental regulators and ubiquitously expressed genes. STARR-seq can be used to identify and quantify enhancer activity in other eukaryotes, including humans.

889 citations