scholarly journals Epigenetic Memory Independent of Symmetric Histone Inheritance

2019 ◽  
Author(s):  
Daniel S Saxton ◽  
Jasper Rine
Keyword(s):  
Gene Regulation ◽  
Dna Replication ◽  
Gene Silencing ◽  
Histone Modifications ◽  
Epigenetic Memory ◽  
Important Form

AbstractHeterochromatic gene silencing is an important form of gene regulation that usually requires specific histone modifications. A popular model posits that inheritance of modified histones, especially in the form of H3-H4 tetramers, underlies inheritance of heterochromatin. Because H3-H4 tetramers are randomly distributed between daughter chromatids during DNA replication, rare occurrences of asymmetric tetramer inheritance within a heterochromatic domain would have the potential to destabilize heterochromatin. This model makes a prediction that shorter heterochromatic domains would experience unbalanced tetramer inheritance more frequently, and thereby be less stable. In contrast to this prediction, we found that shortening a heterochromatic domain in Saccharomyces had no impact on the strength of silencing nor its heritability. Additionally, we found that replisome mutations that disrupt inheritance of H3-H4 tetramers had only minor effects on heterochromatin stability. These findings suggest that histones carry little or no memory of the heterochromatin state through DNA replication.

scholarly journals Epigenetic memory independent of symmetric histone inheritance

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Daniel S Saxton ◽  
Jasper Rine
Keyword(s):  
Gene Regulation ◽  
Dna Replication ◽  
Gene Silencing ◽  
Histone Modifications ◽  
Epigenetic Memory ◽  
Important Form

Heterochromatic gene silencing is an important form of gene regulation that usually requires specific histone modifications. A popular model posits that inheritance of modified histones, especially in the form of H3-H4 tetramers, underlies inheritance of heterochromatin. Because H3-H4 tetramers are randomly distributed between daughter chromatids during DNA replication, rare occurrences of asymmetric tetramer inheritance within a heterochromatic domain would have the potential to destabilize heterochromatin. This model makes a prediction that shorter heterochromatic domains would experience unbalanced tetramer inheritance more frequently, and thereby be less stable. In contrast to this prediction, we found that shortening a heterochromatic domain in Saccharomyces had no impact on the strength of silencing nor its heritability. Additionally, we found that replisome mutations that disrupt inheritance of H3-H4 tetramers had only minor effects on heterochromatin stability. These findings suggest that histones carry little or no memory of the heterochromatin state through DNA replication.

scholarly journals Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory

2017 ◽  
Vol 3 (8) ◽  
pp. e1701143 ◽  
Author(s):  
Adam Klosin ◽  
Kadri Reis ◽  
Cristina Hidalgo-Carcedo ◽  
Eduard Casas ◽  
Tanya Vavouri ◽  
...  
Keyword(s):  
Dna Replication ◽  
Epigenetic Memory

scholarly journals Evolution of DNA Replication Origin Specification and Gene Silencing Mechanisms

2020 ◽  
Author(s):  
Y. Hu ◽  
A. Tareen ◽  
Y-J. Sheu ◽  
W. T. Ireland ◽  
C. Speck ◽  
...  
Keyword(s):  
Dna Replication ◽  
Gene Silencing ◽  
Origin Recognition Complex ◽  
Replication Initiation ◽  
Separate Analysis ◽  
Genome Replication ◽  
Sequence Specificity ◽  
Sequence Motifs ◽  
Origin Firing ◽  
Α Helix

AbstractDNA replication in eukaryotic cells initiates from chromosomal locations, called replication origins, that bind the Origin Recognition Complex (ORC) prior to S phase. Origin establishment is guided by well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. At present, the mechanistic and evolutionary reasons for this difference are unclear. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed, among other things, that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove1. We show that this Orc4 α-helix mediates the sequence-specificity of origins in S. cerevisiae. Specifically, mutations were identified within this α-helix that alter the sequence-dependent activity of individual origins as well as change global genomic origin firing patterns. This was accomplished using a massively parallel origin selection assay analyzed using a custom mutual-information-based modeling approach and a separate analysis of whole-genome replication profiling and statistics. Interestingly, the sequence specificity of DNA replication initiation, as mediated by the Orc4 α-helix, has evolved in close conjunction with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.

scholarly journals Role of histone modifications and early termination in pervasive transcription and antisense-mediated gene silencing in yeast

2014 ◽  
Vol 42 (7) ◽  
pp. 4348-4362 ◽  
Author(s):  
Manuele Castelnuovo ◽  
Judith B. Zaugg ◽  
Elisa Guffanti ◽  
Andrea Maffioletti ◽  
Jurgi Camblong ◽  
...  
Keyword(s):  
Gene Silencing ◽  
Histone Modifications ◽  
Early Termination ◽  
Pervasive Transcription

scholarly journals Role for E2F in Control of Both DNA Replication and Mitotic Functions as Revealed from DNA Microarray Analysis

2001 ◽  
Vol 21 (14) ◽  
pp. 4684-4699 ◽  
Author(s):  
Seiichi Ishida ◽  
Erich Huang ◽  
Harry Zuzan ◽  
Rainer Spang ◽  
Gustavo Leone ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Regulation ◽  
Dna Replication ◽  
Dna Microarrays ◽  
Cell Cycle Analysis ◽  
Cell Synchrony ◽  
Mammalian Cell Cycle ◽  
Induced Genes ◽  
Regulated Gene Expression ◽  
E2f Proteins

ABSTRACT We have used high-density DNA microarrays to provide an analysis of gene regulation during the mammalian cell cycle and the role of E2F in this process. Cell cycle analysis was facilitated by a combined examination of gene control in serum-stimulated fibroblasts and cells synchronized at G1/S by hydroxyurea block that were then released to proceed through the cell cycle. The latter approach (G1/S synchronization) is critical for rigorously maintaining cell synchrony for unambiguous analysis of gene regulation in later stages of the cell cycle. Analysis of these samples identified seven distinct clusters of genes that exhibit unique patterns of expression. Genes tend to cluster within these groups based on common function and the time during the cell cycle that the activity is required. Placed in this context, the analysis of genes induced by E2F proteins identified genes or expressed sequence tags not previously described as regulated by E2F proteins; surprisingly, many of these encode proteins known to function during mitosis. A comparison of the E2F-induced genes with the patterns of cell growth-regulated gene expression revealed that virtually all of the E2F-induced genes are found in only two of the cell cycle clusters; one group was regulated at G1/S, and the second group, which included the mitotic activities, was regulated at G2. The activation of the G2 genes suggests a broader role for E2F in the control of both DNA replication and mitotic activities.

scholarly journals Ash2 acts as an ecdysone receptor coactivator by stabilizing the histone methyltransferase Trr

2013 ◽  
Vol 24 (3) ◽  
pp. 361-372 ◽  
Author(s):  
Albert Carbonell ◽  
Alexander Mazo ◽  
Florenci Serras ◽  
Montserrat Corominas
Keyword(s):  
Gene Regulation ◽  
Histone Modifications ◽  
Transcriptional Activation ◽  
Histone H3 ◽  
Histone Methyltransferase ◽  
Ecdysone Receptor ◽  
Related Protein ◽  
Molting Hormone ◽  
Set Domain ◽  
Present Evidence

The molting hormone ecdysone triggers chromatin changes via histone modifications that are important for gene regulation. On hormone activation, the ecdysone receptor (EcR) binds to the SET domain–containing histone H3 methyltransferase trithorax-related protein (Trr). Methylation of histone H3 at lysine 4 (H3K4me), which is associated with transcriptional activation, requires several cofactors, including Ash2. We find that ash2 mutants have severe defects in pupariation and metamorphosis due to a lack of activation of ecdysone-responsive genes. This transcriptional defect is caused by the absence of the H3K4me3 marks set by Trr in these genes. We present evidence that Ash2 interacts with Trr and is required for its stabilization. Thus we propose that Ash2 functions together with Trr as an ecdysone receptor coactivator.

scholarly journals Evolution of DNA replication origin specification and gene silencing mechanisms

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Y. Hu ◽  
A. Tareen ◽  
Y-J. Sheu ◽  
W. T. Ireland ◽  
C. Speck ◽  
...  
Keyword(s):  
Dna Replication ◽  
Gene Silencing ◽  
Dna Sequence ◽  
Origin Recognition Complex ◽  
Separate Analysis ◽  
Sequence Specificity ◽  
Replication Origins ◽  
Origin Firing ◽  
Dna Sequence Specificity ◽  
Α Helix

Abstract DNA replication in eukaryotic cells initiates from replication origins that bind the Origin Recognition Complex (ORC). Origin establishment requires well-defined DNA sequence motifs in Saccharomyces cerevisiae and some other budding yeasts, but most eukaryotes lack sequence-specific origins. A 3.9 Å structure of S. cerevisiae ORC-Cdc6-Cdt1-Mcm2-7 (OCCM) bound to origin DNA revealed that a loop within Orc2 inserts into a DNA minor groove and an α-helix within Orc4 inserts into a DNA major groove. Using a massively parallel origin selection assay coupled with a custom mutual-information-based modeling approach, and a separate analysis of whole-genome replication profiling, here we show that the Orc4 α-helix contributes to the DNA sequence-specificity of origins in S. cerevisiae and Orc4 α-helix mutations change genome-wide origin firing patterns. The DNA sequence specificity of replication origins, mediated by the Orc4 α-helix, has co-evolved with the gain of ORC-Sir4-mediated gene silencing and the loss of RNA interference.

Sign in / Sign up

Export Citation Format

Share Document