scholarly journals Embryonic transcription is controlled by maternally defined chromatin state

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Saartje Hontelez ◽  
Ila van Kruijsbergen ◽  
Georgios Georgiou ◽  
Simon J. van Heeringen ◽  
Ozren Bogdanovic ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Chromatin State ◽  
Regulatory Sequences ◽  
Maternal Factors ◽  
Maternal Control ◽  
Regulatory Regions ◽  
Zygotic Transcription ◽  
Histone Modifying Enzymes ◽  
Neurula Stage ◽  
P300 Recruitment

Abstract Histone-modifying enzymes are required for cell identity and lineage commitment, however little is known about the regulatory origins of the epigenome during embryonic development. Here we generate a comprehensive set of epigenome reference maps, which we use to determine the extent to which maternal factors shape chromatin state in Xenopus embryos. Using α-amanitin to inhibit zygotic transcription, we find that the majority of H3K4me3- and H3K27me3-enriched regions form a maternally defined epigenetic regulatory space with an underlying logic of hypomethylated islands. This maternal regulatory space extends to a substantial proportion of neurula stage-activated promoters. In contrast, p300 recruitment to distal regulatory regions requires embryonic transcription at most loci. The results show that H3K4me3 and H3K27me3 are part of a regulatory space that exerts an extended maternal control well into post-gastrulation development, and highlight the combinatorial action of maternal and zygotic factors through proximal and distal regulatory sequences.

Unequal cleavage in leech embryos: zygotic transcription is required for correct spindle orientation in subset of early blastomeres

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 599-606
Author(s):  
S.T. Bissen ◽  
C.M. Smith
Keyword(s):  
Cell Division ◽  
Early Period ◽  
Spindle Orientation ◽  
Mitotic Spindles ◽  
Maternal Control ◽  
Transcription Analysis ◽  
Cell Divisions ◽  
Zygotic Transcription ◽  
Different Types ◽  
Alpha Amanitin

Leech embryos undergo invariant sequences of equal and unequal cell divisions to give rise to identifiable progeny cells. While many of the early cleavages are under maternal control, the divisions of a subset of early blastomeres (the large cells of the D' lineage) are perturbed after the inhibition of zygotic transcription. Analysis of the different types of cells produced in embryos injected with the transcriptional inhibitor, alpha-amanitin, revealed that the symmetry of cell division is perturbed in these large D'-derived cells during this early period of development. These cells, which would normally undergo a series of equal and unequal cleavages, always undergo equal cleavages after the inhibition of zygotic transcription. It appears that zygotically transcribed gene product(s) are required in the large cells of the D' lineage to orient the mitotic spindles properly for these unequal cell cleavages.

Control of the expression of the bithorax complex genes abdominal-A and abdominal-B by cis-regulatory regions in Drosophila embryos

Development ◽  
1991 ◽  
Vol 111 (2) ◽  
pp. 437-449 ◽  
Author(s):  
E. Sanchez-Herrero
Keyword(s):  
Regulatory Sequences ◽  
Bithorax Complex ◽  
Regulatory Regions ◽  
Drosophila Embryos

The abdominal-A (abd-A) and Abdominal-B (Abd-B) genes of the bithorax complex (BX-C) specify the identity of most of the Drosophila abdomen. Six different classes of infraabdominal (iab) mutations within the BX-C transform a subset of the parasegments affected by the lack of these two genes. It is thought that these mutations define parasegmental cis-regulatory regions that control the expression of abd-A and Abd-B. By staining embryos mutant for different iab mutations with anti-abd-A and anti-Abd-B antibodies I show here that the expression of Abd-B (and probably also abd-A) exhibit a parasegmental regulation. I have also studied the significance of the chromosomal order of parasegmental iab regulatory sequences, and the possible presence of chromosomal ‘boundaries’ between them, by looking at the expression of abd-A and Abd-B in embryos carrying the Uab and Mcp mutations. These data are discussed in the light of models of parasegmental-specific regulatory regions within the BX-C.

scholarly journals Modeling of Epigenetic Modification-Induced Changes in CRX-dependent Genes cis-Regulatory Elements

2017 ◽  
Author(s):  
Reafa A. Hossain ◽  
Nicholas R. Dunham ◽  
Megan E. Harris ◽  
Taylor L. Hutchinson ◽  
Justin M. Kidd ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Regulation ◽  
Binding Sites ◽  
Epigenetic Modification ◽  
Inverse Correlation ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Regulatory Sequences ◽  
Ocular Tissues ◽  
Regulatory Regions

AbstractPurposeDNA methylation is a well characterized epigenetic repressor of mRNA transcription in many plant and vertebrate systems. However, the mechanism of this repression is not fully understood. The process of synthesizing a strand of RNA from DNA, or transcription, is controlled by proteins that regulate RNA polymerase activity by binding to specific gene regulatory sequences. Cone-rod homeobox (CRX) is a well-characterized mammalian transcription factor that controls photoreceptor cell specific gene expression. While much is known about the functions and DNA binding specificity of CRX, less is known about how DNA methylation modulates CRX binding affinity to genomic cis-regulatory elements.MethodsWe used bisulfite pyrosequencing of human ocular tissues to measure DNA methylation levels of the regulatory regions of RHO, PDE6B, PAX6, and LINE. To describe the molecular mechanism of repression, we used molecular modeling to illustrate the effect of DNA methylation on human RHO regulatory sequences.ResultsIn this study, we demonstrate an inverse correlation between DNA methylation in regulatory regions adjacent to the human RHO and PDE6B genes and their subsequent transcription in human ocular tissues. Docking of CRX to our DNA models shows that CRX interacts with the grooves of these sequences, suggesting changes in groove structure could regulate binding. Molecular dynamics simulations of the RHO promoter and enhancer regions show changes in the flexibility and groove width upon epigenetic modification. Models also demonstrate that changes to the local dynamics of CRX binding sites within RHO regulatory sequences which may account for the repression of CRX dependent transcription.ConclusionCollectively, these data demonstrate epigenetic regulation of CRX binding sites in human retinal tissue and provide insight into the mechanism of this mode of epigenetic regulation to be tested in future experiments.

scholarly journals Maternally inherited piRNAs direct transient heterochromatin formation at active transposons during early Drosophila embryogenesis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Martin H Fabry ◽  
Federica A Falconio ◽  
Fadwa Joud ◽  
Emily K Lythgoe ◽  
Benjamin Czech ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Germ Cells ◽  
Genome Stability ◽  
Mobile Element ◽  
Piwi Protein ◽  
Heterochromatin Formation ◽  
Zygotic Transcription ◽  
Time Required ◽  
Pirna Pathway ◽  
Genome Activation

The PIWI-interacting RNA (piRNA) pathway controls transposon expression in animal germ cells, thereby ensuring genome stability over generations. In Drosophila, piRNAs are intergenerationally inherited through the maternal lineage, and this has demonstrated importance in the specification of piRNA source loci and in silencing of I- and P-elements in the germ cells of daughters. Maternally inherited Piwi protein enters somatic nuclei in early embryos prior to zygotic genome activation and persists therein for roughly half of the time required to complete embryonic development. To investigate the role of the piRNA pathway in the embryonic soma, we created a conditionally unstable Piwi protein. This enabled maternally deposited Piwi to be cleared from newly laid embryos within 30 minutes and well ahead of the activation of zygotic transcription. Examination of RNA and protein profiles over time, and correlation with patterns of H3K9me3 deposition, suggests a role for maternally deposited Piwi in attenuating zygotic transposon expression in somatic cells of the developing embryo. In particular, robust deposition of piRNAs targeting roo, an element whose expression is mainly restricted to embryonic development, results in the deposition of transient heterochromatic marks at active roo insertions. We hypothesize that roo, an extremely successful mobile element, may have adopted a lifestyle of expression in the embryonic soma to evade silencing in germ cells.

The evolution of genomic imprinting

Development ◽  
1990 ◽  
Vol 108 (Supplement) ◽  
pp. 47-53
Author(s):  
H. Sharat Chandra ◽  
Vidyanand Nanjundiah
Keyword(s):  
Sex Determination ◽  
Genomic Imprinting ◽  
Potential Role ◽  
Fragile X ◽  
Chromosome Elimination ◽  
Regulatory Sequences ◽  
Maternal Control ◽  
Fitness Effects ◽  
Gene Copies ◽  
Offspring Sex

We explore three possible pathways for the evolution of genomic imprinting. (1) Imprinting may be advantageous in itself when imprinted and unimprinted alleles of a locus confer different phenotypes. If a segment of DNA is imprinted in the gametes of one sex but not in those of the other, it might lead to effects correlated with sexual dimorphism. More fundamentally, in certain organisms, sex determination might have evolved because of imprinting. When imprinting leads to chromosome elimination or inactivation and occurs in some embryos but not in others, two classes of embryos, differing in the number of functional gene copies, would result. A model for sex determination based on inequality in the actual or effective copy-number of particular noncoding, regulatory sequences of DNA has been proposed (Chandra, Proc. natn. Acad. Sci. U.S.A. 82. 1165–1169 and 6947–6949, 1985). Maternal control of offspring sex is another possible consequence of imprinting; this would indicate a potential role for imprinting in sex ratio evolution. (2) Genes responsible for imprinting may have pleiotropic effects and they may have been selected for reasons other than their imprinting ability. Lack of evidence precludes further consideration of this possibility. (3) Imprinting could have co-evolved with other traits. For instance, gamete-specific imprinting could lead to a lowered fitness of androgenetic or gynogenetic diploids relative to the fitness of ‘normal’ diploids. This in turn would reinforce the evolution of anisogamy. The reversibility of imprinting raises the possibility of occasional incomplete or improper erasure. If the site of imprinting is the egg – as appears to be the case with the human X (Chandra and Brown, Nature 253. 165–168, 1975) – either improper imprinting or improper erasure could lead to unusual patterns of inheritance (as in the fragile-X syndrome) or fitness effects skipping generations.

Regulation of human embryonic globin genes zeta 2 and epsilon in stably transformed mouse erythroleukemia cells

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1832-1837 ◽  
Author(s):  
P Vyas ◽  
JA Sharpe ◽  
P Watt ◽  
DR Higgs ◽  
WG Wood
Keyword(s):  
Regulatory Elements ◽  
Erythroid Cell ◽  
Regulatory Sequences ◽  
Globin Genes ◽  
Promoter Regions ◽  
Regulatory Regions ◽  
Chromosomal Organization ◽  
Erythroleukemia Cells ◽  
Cast Doubt ◽  
Mouse Erythroleukemia

Previous work has suggested that the promoter regions of the human embryonic zeta 2 and epsilon globin genes contain negative regulatory regions that could play a role in the repression of these genes in postembryonic erythroblasts. We have examined this possibility by studying the expression of these genes in mouse erythroleukemia cells, an adult erythroid cell line that might be expected to contain repressor molecules that would bind to the putative negative regulatory regions. When attached to appropriate upstream regulatory elements (alpha HS-40 and beta HS1,2) both the zeta and epsilon genes were expressed in these cells at a low level, but no increase in expression was observed when similar constructs lacking the proposed negative regulatory sequences were introduced into these cells. These results cast doubt on the possibility that these sequences play a major role in the developmental repression of the embryonic globin genes, unless they function only in a normal chromosomal organization.

scholarly journals Regulation of human embryonic globin genes zeta 2 and epsilon in stably transformed mouse erythroleukemia cells

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1832-1837 ◽  
Author(s):  
P Vyas ◽  
JA Sharpe ◽  
P Watt ◽  
DR Higgs ◽  
WG Wood
Keyword(s):  
Regulatory Elements ◽  
Erythroid Cell ◽  
Regulatory Sequences ◽  
Globin Genes ◽  
Promoter Regions ◽  
Regulatory Regions ◽  
Chromosomal Organization ◽  
Erythroleukemia Cells ◽  
Cast Doubt ◽  
Mouse Erythroleukemia

Abstract Previous work has suggested that the promoter regions of the human embryonic zeta 2 and epsilon globin genes contain negative regulatory regions that could play a role in the repression of these genes in postembryonic erythroblasts. We have examined this possibility by studying the expression of these genes in mouse erythroleukemia cells, an adult erythroid cell line that might be expected to contain repressor molecules that would bind to the putative negative regulatory regions. When attached to appropriate upstream regulatory elements (alpha HS-40 and beta HS1,2) both the zeta and epsilon genes were expressed in these cells at a low level, but no increase in expression was observed when similar constructs lacking the proposed negative regulatory sequences were introduced into these cells. These results cast doubt on the possibility that these sequences play a major role in the developmental repression of the embryonic globin genes, unless they function only in a normal chromosomal organization.

scholarly journals UNDERSTANDING DISTAL TRANSCRIPTIONAL REGULATION FROM SEQUENCE, EXPRESSION AND INTERACTOME PERSPECTIVES

2010 ◽  
Vol 08 (02) ◽  
pp. 219-246 ◽  
Author(s):  
ARVIND RAO ◽  
DAVID J. STATES ◽  
ALFRED O. HERO ◽  
JAMES DOUGLAS ENGEL
Keyword(s):  
Computational Biology ◽  
De Novo ◽  
Sequence Data ◽  
Regulatory Elements ◽  
Proximal Promoter ◽  
Regulatory Sequences ◽  
Sequence Motifs ◽  
Specific Sequence ◽  
Specific Expression ◽  
Regulatory Regions

Gene regulation in eukaryotes involves a complex interplay between the proximal promoter and distal genomic elements (such as enhancers) which work in concert to drive precise spatio-temporal gene expression. The experimental localization and characterization of gene regulatory elements is a very complex and resource-intensive process. The computational identification of regulatory regions that confer spatiotemporally specific tissue-restricted expression of a gene is thus an important challenge for computational biology. One of the most popular strategies for enhancer localization from DNA sequence is the use of conservation-based prefiltering and more recently, the use of canonical (transcription factor motifs) or de novo tissue-specific sequence motifs. However, there is an ongoing effort in the computational biology community to further improve the fidelity of enhancer predictions from sequence data by integrating other, complementary genomic modalities. In this work, we propose a framework that complements existing methodologies for prospective enhancer identification. The methods in this work are derived from two key insights: (i) that chromatin modification signatures can discriminate proximal and distally located regulatory regions and (ii) the notion of promoter-enhancer cross-talk (as assayed in 3C/5C experiments) might have implications in the search for regulatory sequences that co-operate with the promoter to yield tissue-restricted, gene-specific expression.

scholarly journals Discovering single nucleotide variants and indels from bulk and single-cell ATAC-seq

2021 ◽  
Author(s):  
Arya R. Massarat ◽  
Arko Sen ◽  
Jeff Jaureguy ◽  
Sélène T. Tyndale ◽  
Yi Fu ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Single Cell ◽  
Genome Sequencing ◽  
Superior Performance ◽  
Whole Genome Sequencing Data ◽  
Regulatory Sequences ◽  
Whole Genome ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Regulatory Regions

ABSTRACTGenetic variants and de novo mutations in regulatory regions of the genome are typically discovered by whole-genome sequencing (WGS), however WGS is expensive and most WGS reads come from non-regulatory regions. The Assay for Transposase-Accessible Chromatin (ATAC-seq) generates reads from regulatory sequences and could potentially be used as a low-cost ‘capture’ method for regulatory variant discovery, but its use for this purpose has not been systematically evaluated. Here we apply seven variant callers to bulk and single-cell ATAC-seq data and evaluate their ability to identify single nucleotide variants (SNVs) and insertions/deletions (indels). In addition, we develop an ensemble classifier, VarCA, which combines features from individual variant callers to predict variants. The Genome Analysis Toolkit (GATK) is the best-performing individual caller with precision/recall on a bulk ATAC test dataset of 0.92/0.97 for SNVs and 0.87/0.82 for indels. On bulk ATAC-seq reads, VarCA achieves superior performance with precision/recall of 0.99/0.95 for SNVs and 0.93/0.80 for indels. On single-cell ATAC-seq reads, VarCA attains precision/recall of 0.98/0.94 for SNVs and 0.82/0.82 for indels. In summary, ATAC-seq reads can be used to accurately discover non-coding regulatory variants in the absence of whole-genome sequencing data and our ensemble method, VarCA, has the best overall performance.

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