Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster.
Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.
Section of Developmental Genomics, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Hangnoh
H
Lee
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.
Dong-Yeon
DY
Cho
Section of Developmental Genomics, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.|Department of Biology, Indiana University, Bloomington, Indiana, United States of America.
Cale
0000-0003-1963-5850
C
Whitworth
Department of Biology, Indiana University, Bloomington, Indiana, United States of America.
Robert
0000-0002-4126-9116
R
Eisman
Department of Biology, Indiana University, Bloomington, Indiana, United States of America.
Melissa
0000-0002-4636-4024
M
Phelps
Department of Genetics and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
John
J
Roote
Department of Biology, Indiana University, Bloomington, Indiana, United States of America.
Thomas
T
Kaufman
Department of Biology, Indiana University, Bloomington, Indiana, United States of America.
Kevin
K
Cook
Department of Genetics and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
Steven
0000-0003-0546-3031
S
Russell
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.
Teresa
T
Przytycka
Section of Developmental Genomics, Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Kidney and Digestive Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Brian
B
Oliver
D000818:Animals; D002843:Chromatin / Q000235:genetics*; D056905:Chromosome Breakpoints; D059006:Chromosomes, Insect / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D017353:Gene Deletion; D018628:Gene Dosage; D053263:Gene Regulatory Networks
D002843:Chromatin