scholarly journals The H4K20 demethylase DPY-21 regulates the dynamics of condensin DC binding

2021 ◽  
Author(s):  
Laura Breimann ◽  
Ana Karina Morao ◽  
Jun Kim ◽  
David Sebastian Jimenez ◽  
Nina Maryn ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Transcriptional Repression ◽  
Fluorescence Recovery After Photobleaching ◽  
Null Mutant ◽  
Wild Type ◽  
X Chromosomes ◽  
C Elegans ◽  
Catalytic Role ◽  
Mobile Fraction

Condensin is a multi-subunit SMC complex that binds to and compacts chromosomes. Here we addressed the regulation of condensin binding dynamics using C. elegans condensin DC, which represses X chromosomes in hermaphrodites for dosage compensation. We established fluorescence recovery after photobleaching (FRAP) using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes its binding. Next, we performed FRAP in the background of several chromatin modifier mutants that cause varying degrees of X-chromosome derepression. The greatest effect was in a null mutant of the H4K20me2 demethylase DPY-21, where the mobile fraction of condensin DC reduced from ∼30% to 10%. In contrast, a catalytic mutant of dpy-21 did not regulate condensin DC mobility. Hi-C data in the dpy-21 null mutant showed little change compared to wild type, uncoupling Hi-C measured long-range DNA contacts from transcriptional repression of the X chromosomes. Together, our results indicate that DPY-21 has a non-catalytic role in regulating the dynamics of condensin DC binding, which is important for transcription repression.

scholarly journals A noncatalytic activity of the H4K20 demethylase DPY-21 regulates condensin DC binding

2021 ◽  
Author(s):  
Laura Breimann ◽  
Ana Karina Morao ◽  
Jun Kim ◽  
David Jimenez ◽  
Nina Maryn ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Dosage Compensation ◽  
Fluorescence Recovery After Photobleaching ◽  
Null Mutant ◽  
X Chromosomes ◽  
Mobility Separation ◽  
C Elegans ◽  
Catalytic Role ◽  
Mobile Fraction

Condensin is a multi-subunit SMC complex that binds to and compacts chromosomes. Unlike cohesin, in vivo regulators of condensin binding dynamics remain unclear. Here we addressed this question using C. elegans condensin DC, which specifically binds to and represses transcription of both X chromosomes in hermaphrodites for dosage compensation. Mutants of several chromatin modifiers that regulate H4K20me and H4K16ac cause varying degrees of X chromosome derepression. We used fluorescence recovery after photobleaching (FRAP) to analyze how these modifiers regulate condensin DC binding dynamics in vivo. We established FRAP using the SMC4 homolog DPY-27 and showed that a well-characterized ATPase mutation abolishes its binding. The greatest effect on condensin DC dynamics was in a null mutant of the H4K20me2 demethylase DPY-21, where the mobile fraction of the complex reduced from ~30% to 10%. In contrast, a catalytic mutant of dpy-21 did not regulate condensin DC mobility. Separation of catalytic and non-catalytic activity is also supported by Hi-C data in the dpy-21 null mutant. Together, our results indicate that DPY-21 has a non-catalytic role in regulating the dynamics of condensin DC binding, which is important for transcription repression.

SDC-3 coordinates the assembly of a dosage compensation complex on the nematode X chromosome

Development ◽  
1997 ◽  
Vol 124 (5) ◽  
pp. 1019-1031 ◽  
Author(s):  
T.L. Davis ◽  
B.J. Meyer
Keyword(s):  
Zinc Finger ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Protein Complex ◽  
Terminal Region ◽  
X Chromosomes ◽  
C Elegans ◽  
Amino Terminal ◽  
Zinc Finger Motifs ◽  
Specific Association

X chromosome expression in C. elegans is controlled by a chromosome-wide regulatory process called dosage compensation that specifically reduces by half the level of transcripts made from each hermaphrodite X chromosome. This process equalizes X expression between the sexes (XX hermaphrodites and XO males), despite their two-fold difference in X chromosome dose, and thereby prevents sex-specific lethality. Dosage compensation is achieved by a protein complex that associates with X in a sex-specific fashion to modulate gene expression. SDC-3, a protein that coordinately controls both sex determination and dosage compensation, activates dosage compensation by directing the dosage compensation protein complex to the hermaphrodite X chromosomes. We show that SDC-3 coordinates this assembly through its own sex-specific association with X. SDC-3 in turn requires other members of the dosage compensation gene hierarchy for its stability and its X localization. In addition, SDC-3 requires its own zinc finger motifs and an amino-terminal region for its X association. Our experiments suggest the possible involvement of zinc finger motifs in X chromosome recognition and the amino-terminal region in interactions with other dosage compensation proteins.

scholarly journals Attempts to test the inactive-X theory of dosage compensation in mammals

1963 ◽  
Vol 4 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Mary F. Lyon
Keyword(s):  
X Chromosome ◽  
Adult Female ◽  
Dosage Compensation ◽  
Somatic Cells ◽  
Coat Colour ◽  
The Other ◽  
Wild Type ◽  
X Chromosomes ◽  
Female Mice ◽  
Colour Mutant

The inactive-X theory of dosage compensation postulates that in all somatic cells of adult female mammals one or other of the two X chromosomes is genetically inactive. This means that in a female heterozygous for two non-allelic genes acting through the same cells, and carried one on each X chromosome, one or other gene should act in all cells. Conversely, if the two genes are carried on the same X, then both genes should act in some cells and neither gene in the remainder. This point has been tested by breeding experiments with mice, using pairs of genes affecting coat colour and coat texture. In female mice carrying the colour mutant dappled, Modp, on one X and a translocation including the wild-type alleles of pink-eye, p, and albino, c, on the other, either Modp or the translocation acted in all cells. With the genes tabby, Ta and striated, Str, affecting coat texture, in Str + / + Ta females tabby acted only in the non-Str patches, while in StrTa/ + + it acted only in the Str ones. Thus these experiments confirm that only one of the two X chromosomes is active in the somatic cells of female mammals.

scholarly journals Dual Roles for Nuclear RNAi Argonautes in C. elegans Dosage Compensation

2021 ◽  
Author(s):  
Michael B Davis ◽  
Bahaar Chawla ◽  
Eshna Jash ◽  
Lillian E. Tushman ◽  
Rebecca A. Haines ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Dual Roles ◽  
Independent Manner ◽  
X Chromosomes ◽  
C Elegans ◽  
Gene Regulatory ◽  
Subsequent Activation ◽  
Nuclear Rnai ◽  
Transcriptional Output

Dosage compensation involves chromosome-wide gene regulatory mechanisms which impact higher order chromatin structure and are crucial for organismal health. Using a genetic approach, we identified Argonaute genes which promote dosage compensation in C. elegans. Dosage compensation in C. elegans hermaphrodites is initiated by the silencing of xol-1 and subsequent activation of the Dosage Compensation Complex (DCC) which binds to both hermaphrodite X chromosomes and reduces transcriptional output by twofold. A hallmark phenotype of dosage compensation mutants is decondensation of the X chromosomes. We characterized this phenotype in Argonaute mutants using X chromosome paint probe and fluorescence microscopy. We found that while nuclear Argonaute mutants hrde-1 and nrde-3 exhibit de-repression of xol-1 transcripts, they also effect X chromosome condensation in a xol-1-independent manner. We also characterized the physiological contribution of Argonaute genes to dosage compensation using genetic assays and find that hrde-1 and nrde-3, together with the piRNA Argonaute prg-1, contribute to healthy dosage compensation both upstream and downstream of xol-1.

scholarly journals Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoma Ota ◽  
Makoto Hayashi ◽  
Shumpei Morita ◽  
Hiroki Miura ◽  
Satoru Kobayashi
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Primordial Germ Cells ◽  
Histone H4 ◽  
X Chromosomes ◽  
Essential Components ◽  
Msl Complex ◽  
Male Specific

AbstractDosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

scholarly journals Parallel Universes for Models of X Chromosome Dosage Compensation in Drosophila: A Review

2016 ◽  
Vol 148 (1) ◽  
pp. 52-67 ◽  
Author(s):  
James A. Birchler
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Fold Increase ◽  
Molecular Data ◽  
X Chromosomes ◽  
Histone Modifiers ◽  
Parallel Universes ◽  
Msl Complex ◽  
High Level

Dosage compensation in Drosophila involves an approximately 2-fold increase in expression of the single X chromosome in males compared to the per gene expression in females with 2 X chromosomes. Two models have been considered for an explanation. One proposes that the male-specific lethal (MSL) complex that is associated with the male X chromosome brings histone modifiers to the sex chromosome to increase its expression. The other proposes that the inverse effect which results from genomic imbalance would tend to upregulate the genome approximately 2-fold, but the MSL complex sequesters histone modifiers from the autosomes to the X to mute this autosomal male-biased expression. On the X, the MSL complex must override the high level of resulting histone modifications to prevent overcompensation of the X chromosome. Each model is evaluated in terms of fitting classical genetic and recent molecular data. Potential paths toward resolving the models are suggested.

scholarly journals Developmental Dynamics of X-Chromosome Dosage Compensation by the DCC and H4K20me1 in C. elegans

PLoS Genetics ◽  
2015 ◽  
Vol 11 (12) ◽  
pp. e1005698 ◽  
Author(s):  
Maxwell Kramer ◽  
Anna-Lena Kranz ◽  
Amanda Su ◽  
Lara H. Winterkorn ◽  
Sarah Elizabeth Albritton ◽  
...  
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
C Elegans ◽  
Developmental Dynamics

scholarly journals Gene action in the mammalian X-chromosome

1967 ◽  
Vol 9 (3) ◽  
pp. 343-357 ◽  
Author(s):  
Hans Grüneberg
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Gene Action ◽  
X Chromosomes ◽  
Independent Evidence ◽  
Partial Inhibition ◽  
Lyon Hypothesis ◽  
New Hypothesis

Contrary to opinions expressed by various authors, the phenotype of heterozygotes for mammalian sex-linked genes gives no support for the Lyon hypothesis (L.H.). Evidence, mainly from the mouse, shows that in such heterozygotes, both alleles act together as in autosomal genes.In the present paper, it is shown that neither the behaviour of double heterozygotes for sex-linked genes nor that of X-autosome translocations provides independent evidence in favour of the L.H.: in each case, the interpretation depends on that of the behaviour of single heterozygotes and hence fails to discriminate. Moreover, new facts from both types of situation are also contrary to the L.H. In particular, a unified interpretation which fits the behaviour of genes in all known types of X-autosome translocations in the mouse requires the assumption that partial inhibition of gene action happens in both X-chromosomes of mouse females, and presumably the females of other mammals. The new hypothesis is consistent with all relevant genetical facts and, like the L.H., it also accounts for dosage compensation.

scholarly journals The Caenorhabditis elegans Replication Licensing Factor CDT-1 Is Targeted for Degradation by the CUL-4/DDB-1 Complex

2006 ◽  
Vol 27 (4) ◽  
pp. 1394-1406 ◽  
Author(s):  
Youngjo Kim ◽  
Edward T. Kipreos
Keyword(s):  
Caenorhabditis Elegans ◽  
Ubiquitin Ligase ◽  
S Phase ◽  
Null Mutant ◽  
Wild Type ◽  
C Elegans ◽  
Licensing Factor ◽  
Ubiquitin Ligase E3 ◽  
Blast Cells ◽  
Temporal Restriction

ABSTRACT The replication of genomic DNA is strictly regulated to occur only once per cell cycle. This regulation centers on the temporal restriction of replication licensing factor activity. Two distinct ubiquitin ligase (E3) complexes, CUL4/DDB1 and SCFSkp2, have been reported to target the replication licensing factor Cdt1 for ubiquitin-mediated proteolysis. However, it is unclear to what extent these two distinct Cdt1 degradation pathways are conserved. Here, we show that Caenorhabditis elegans DDB-1 is required for the degradation of CDT-1 during S phase. DDB-1 interacts specifically with CUL-4 but not with other C. elegans cullins. A ddb-1 null mutant exhibits extensive DNA rereplication in postembryonic BLAST cells, similar to what is observed in cul-4(RNAi) larvae. DDB-1 physically associates with CDT-1, suggesting that CDT-1 is a direct substrate of the CUL-4/DDB-1 E3 complex. In contrast, a deletion mutant of the C. elegans Skp2 ortholog, skpt-1, appears overtly wild type with the exception of an impenetrant gonad migration defect. There is no appreciable role for SKPT-1 in the degradation of CDT-1 during S phase, even in a sensitized ddb-1 mutant background. We propose that the CUL-4/DDB-1 ubiquitin ligase is the principal E3 for regulating the extent of DNA replication in C. elegans.

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