[Report] Transposition-Driven Genomic Heterogeneity in the Drosophila Brain: Transposon movement in memory-relevant neurons in fruit flies increases neuronal diversity within and between animals.
Authors: Paola N. Perrat, Shamik DasGupta, Jie Wang, William Theurkauf, Zhiping Weng, Michael Rosbash, Scott Waddell
Justin Crocker's reading list...
Thursday, April 4, 2013
[Report] Drosophila H1 Regulates the Genetic Activity of Heterochromatin by Recruitment of Su(var)3-9
[Report] Drosophila H1 Regulates the Genetic Activity of Heterochromatin by Recruitment of Su(var)3-9: The “fifth” histone, H1, acts to recruit a histone-methylating enzyme to silence specific regions of the genome.
Authors: Xingwu Lu, Sandeep N. Wontakal, Harsh Kavi, Byung Ju Kim, Paloma M. Guzzardo, Alexander V. Emelyanov, Na Xu, Gregory J. Hannon, Jiri Zavadil, Dmitry V. Fyodorov, Arthur I. Skoultchi
Authors: Xingwu Lu, Sandeep N. Wontakal, Harsh Kavi, Byung Ju Kim, Paloma M. Guzzardo, Alexander V. Emelyanov, Na Xu, Gregory J. Hannon, Jiri Zavadil, Dmitry V. Fyodorov, Arthur I. Skoultchi
Wednesday, April 3, 2013
Why I Study Duck Genitalia
Why I Study Duck Genitalia:
In the past few days, the Internet has been filled with commentary on whether the National Science Foundation should have paid for my study on duck genitalia, and 88.7 percent of respondents to a Fox news online poll agreed that studying duck genitalia is wasteful government spending. The commentary supporting and decrying the study continues to grow. As the lead investigator in this research, I would like to weigh in on the controversy and offer some insights into the process of research funding by the NSF.
In the past few days, the Internet has been filled with commentary on whether the National Science Foundation should have paid for my study on duck genitalia, and 88.7 percent of respondents to a Fox news online poll agreed that studying duck genitalia is wasteful government spending. The commentary supporting and decrying the study continues to grow. As the lead investigator in this research, I would like to weigh in on the controversy and offer some insights into the process of research funding by the NSF.
Tuesday, April 2, 2013
Promoter Sequence Determines the Relationship between Expression Level and Noise
Promoter Sequence Determines the Relationship between Expression Level and Noise:
by Lucas B. Carey, David van Dijk, Peter M. A. Sloot, Jaap A. Kaandorp, Eran Segal
The ability of cells to accurately control gene expression levels in response to extracellular cues is limited by the inherently stochastic nature of transcriptional regulation. A change in transcription factor (TF) activity results in changes in the expression of its targets, but the way in which cell-to-cell variability in expression (noise) changes as a function of TF activity, and whether targets of the same TF behave similarly, is not known. Here, we measure expression and noise as a function of TF activity for 16 native targets of the transcription factor Zap1 that are regulated by it through diverse mechanisms. For most activated and repressed Zap1 targets, noise decreases as expression increases. Kinetic modeling suggests that this is due to two distinct Zap1-mediated mechanisms that both change the frequency of transcriptional bursts. Notably, we found that another mechanism of repression by Zap1, which is encoded in the promoter DNA, likely decreases the size of transcriptional bursts, producing a unique transcriptional state characterized by low expression and low noise. In addition, we find that further reduction in noise is achieved when a single TF both activates and represses a single target gene. Our results suggest a global principle whereby at low TF concentrations, the dominant source of differences in expression between promoters stems from differences in burst frequency, whereas at high TF concentrations differences in burst size dominate. Taken together, we show that the precise amount by which noise changes with expression is specific to the regulatory mechanism of transcription and translation that acts at each gene.
by Lucas B. Carey, David van Dijk, Peter M. A. Sloot, Jaap A. Kaandorp, Eran Segal
The ability of cells to accurately control gene expression levels in response to extracellular cues is limited by the inherently stochastic nature of transcriptional regulation. A change in transcription factor (TF) activity results in changes in the expression of its targets, but the way in which cell-to-cell variability in expression (noise) changes as a function of TF activity, and whether targets of the same TF behave similarly, is not known. Here, we measure expression and noise as a function of TF activity for 16 native targets of the transcription factor Zap1 that are regulated by it through diverse mechanisms. For most activated and repressed Zap1 targets, noise decreases as expression increases. Kinetic modeling suggests that this is due to two distinct Zap1-mediated mechanisms that both change the frequency of transcriptional bursts. Notably, we found that another mechanism of repression by Zap1, which is encoded in the promoter DNA, likely decreases the size of transcriptional bursts, producing a unique transcriptional state characterized by low expression and low noise. In addition, we find that further reduction in noise is achieved when a single TF both activates and represses a single target gene. Our results suggest a global principle whereby at low TF concentrations, the dominant source of differences in expression between promoters stems from differences in burst frequency, whereas at high TF concentrations differences in burst size dominate. Taken together, we show that the precise amount by which noise changes with expression is specific to the regulatory mechanism of transcription and translation that acts at each gene.
Is junk DNA bunk? [Evolution]
Is junk DNA bunk? [Evolution]: Do data from the Encyclopedia Of DNA Elements (ENCODE) project render the notion of junk DNA obsolete? Here, I review older arguments for junk grounded in the C-value paradox and propose a thought experiment to challenge ENCODE’s ontology. Specifically, what would we expect for the number of functional elements (as...
The Border Between the Ultrabithorax and abdominal-A Regulatory Domains in the Drosophila Bithorax Complex [Gene Expression]
The Border Between the Ultrabithorax and abdominal-A Regulatory Domains in the Drosophila Bithorax Complex [Gene Expression]:
The bithorax complex in Drosophila melanogaster includes three homeobox-containing genes—Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B)—which are required for the proper differentiation of the posterior 10 segments of the body. Each of these genes has multiple distinct regulatory regions; there is one for each segmental unit of the body plan where the genes are expressed. One additional protein- coding gene in the bithorax complex, Glut3, a sugar-transporter homolog, can be deleted without phenotype. We focus here on the upstream regulatory region for Ubx, the bithoraxoid (bxd) domain, and its border with the adjacent infraabdominal-2 (iab-2) domain, which controls abdA. These two domains can be defined by the phenotypes of rearrangement breakpoints, and by the expression patterns of enhancer traps. In D. virilis, the homeotic cluster is split between Ubx and abd-A, and so the border can also be located by a sequence comparison between species. When the border region is deleted in melanogaster, the flies show a dominant phenotype called Front-ultraabdominal (Fub); the first abdominal segment is transformed into a copy of the second abdominal segment. Thus, the border blocks the spread of activation from the bxd domain into the iab-2 domain.
The bithorax complex in Drosophila melanogaster includes three homeobox-containing genes—Ultrabithorax (Ubx), abdominal-A (abd-A), and Abdominal-B (Abd-B)—which are required for the proper differentiation of the posterior 10 segments of the body. Each of these genes has multiple distinct regulatory regions; there is one for each segmental unit of the body plan where the genes are expressed. One additional protein- coding gene in the bithorax complex, Glut3, a sugar-transporter homolog, can be deleted without phenotype. We focus here on the upstream regulatory region for Ubx, the bithoraxoid (bxd) domain, and its border with the adjacent infraabdominal-2 (iab-2) domain, which controls abdA. These two domains can be defined by the phenotypes of rearrangement breakpoints, and by the expression patterns of enhancer traps. In D. virilis, the homeotic cluster is split between Ubx and abd-A, and so the border can also be located by a sequence comparison between species. When the border region is deleted in melanogaster, the flies show a dominant phenotype called Front-ultraabdominal (Fub); the first abdominal segment is transformed into a copy of the second abdominal segment. Thus, the border blocks the spread of activation from the bxd domain into the iab-2 domain.
Monday, April 1, 2013
Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development
Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development:
Co-option of cis-regulatory modules has been suggested as a mechanism for the evolution of expression sites during development. However, the extent and mechanisms involved in mobilization of cis-regulatory modules remains elusive. To trace the history of non-coding elements, which may represent candidate ancestral cis-regulatory modules affirmed during chordate evolution, we have searched for conserved elements in tunicate and vertebrate (Olfactores) genomes. We identified, for the first time, 183 non-coding sequences that are highly conserved between the two groups. Our results show that all but one element are conserved in non-syntenic regions between vertebrate and tunicate genomes, while being syntenic among vertebrates. Nevertheless, in all the groups, they are significantly associated with transcription factors showing specific functions fundamental to animal development, such as multicellular organism development and sequence-specific DNA binding. The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as ‘Olfactores conserved non-coding elements’.
Co-option of cis-regulatory modules has been suggested as a mechanism for the evolution of expression sites during development. However, the extent and mechanisms involved in mobilization of cis-regulatory modules remains elusive. To trace the history of non-coding elements, which may represent candidate ancestral cis-regulatory modules affirmed during chordate evolution, we have searched for conserved elements in tunicate and vertebrate (Olfactores) genomes. We identified, for the first time, 183 non-coding sequences that are highly conserved between the two groups. Our results show that all but one element are conserved in non-syntenic regions between vertebrate and tunicate genomes, while being syntenic among vertebrates. Nevertheless, in all the groups, they are significantly associated with transcription factors showing specific functions fundamental to animal development, such as multicellular organism development and sequence-specific DNA binding. The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as ‘Olfactores conserved non-coding elements’.
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