scholarly journals A conserved function for pericentromeric satellite DNA

2018 ◽  
Author(s):  
Madhav Jagannathan ◽  
Ryan Cummings ◽  
Yukiko M. Yamashita
Keyword(s):  
Cell Death ◽  
Dna Binding ◽  
Satellite Dna ◽  
Interphase Nucleus ◽  
Underlying Mechanism ◽  
Dna Binding Proteins ◽  
Eukaryotic Cells ◽  
Evolutionarily Conserved ◽  
Full Complement ◽  
Single Nucleus

AbstractA universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi AT-hook satellite DNA binding proteins, D. melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into ‘chromocenters’, a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding off of interphase nucleus and cell death. We propose that chromocenter and satellite DNA serves a fundamental role to achieve the universal characteristic of eukaryotic cells: full complement of the genome within a single nucleus.

scholarly journals A conserved function for pericentromeric satellite DNA

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Madhav Jagannathan ◽  
Ryan Cummings ◽  
Yukiko M Yamashita
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Satellite Dna ◽  
Interphase Nucleus ◽  
Underlying Mechanism ◽  
Dna Binding Proteins ◽  
Eukaryotic Cells ◽  
Evolutionarily Conserved ◽  
Full Complement ◽  
Single Nucleus

A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here, we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi-AT-hook satellite DNA-binding proteins, Drosophila melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into ‘chromocenters’, a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding from the interphase nucleus, DNA damage and cell death. We propose that chromocenter and satellite DNA serve a fundamental role in encapsulating the full complement of the genome within a single nucleus, the universal characteristic of eukaryotic cells.

scholarly journals The modular mechanism of chromocenter formation in Drosophila

2018 ◽  
Author(s):  
Madhav Jagannathan ◽  
Ryan Cummings ◽  
Yukiko M. Yamashita
Keyword(s):  
Dna Binding ◽  
Satellite Dna ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Dna Repeats ◽  
Satellite Dnas ◽  
Modular Network ◽  
Full Complement ◽  
Single Nucleus ◽  
Nuclear Structures

AbstractA central principle underlying the ubiquity and abundance of pericentromeric satellite DNA repeats in eukaryotes has remained poorly understood. In our previous study (Jagannathan et al., 2018), we proposed that the interchromosomal clustering of satellite DNAs into nuclear structures known as chromocenters ensures encapsulation of all chromosomes into a single nucleus. Chromocenter disruption led to micronuclei formation, resulting in cell death. Here we show that chromocenter formation is mediated by a ‘modular’ network, where interactions between two sequence-specific satellite DNA-binding proteins, D1 and Prod, bound to their cognate satellite DNAs, bring the full complement of chromosomes into the chromocenter. D1 prod double mutants die during embryogenesis, exhibiting enhanced phenotypes associated with chromocenter disruption, revealing the universal importance of satellite DNAs and chromocenters. Taken together, we propose that interactions between chromocenter modules, consisting of satellite DNA binding proteins and their cognate satellite DNA, package the Drosophila genome within a single nucleus.

scholarly journals The modular mechanism of chromocenter formation in Drosophila

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Madhav Jagannathan ◽  
Ryan Cummings ◽  
Yukiko M Yamashita
Keyword(s):  
Dna Binding ◽  
Satellite Dna ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Drosophila Genome ◽  
Dna Repeats ◽  
Satellite Dnas ◽  
Full Complement ◽  
Single Nucleus ◽  
Nuclear Structures

A central principle underlying the ubiquity and abundance of pericentromeric satellite DNA repeats in eukaryotes has remained poorly understood. Previously we proposed that the interchromosomal clustering of satellite DNAs into nuclear structures known as chromocenters ensures encapsulation of all chromosomes into a single nucleus (Jagannathan et al., 2018). Chromocenter disruption led to micronuclei formation, resulting in cell death. Here we show that chromocenter formation is mediated by a ‘modular’ network, where associations between two sequence-specific satellite DNA-binding proteins, D1 and Prod, bound to their cognate satellite DNAs, bring the full complement of chromosomes into the chromocenter. D1 prod double mutants die during embryogenesis, exhibiting enhanced phenotypes associated with chromocenter disruption, revealing the universal importance of satellite DNAs and chromocenters. Taken together, we propose that associations between chromocenter modules, consisting of satellite DNA binding proteins and their cognate satellite DNA, package the Drosophila genome within a single nucleus.

scholarly journals Variable Requirements for DNA-Binding Proteins at Polycomb-Dependent Repressive Regions in Human HOX Clusters

2013 ◽  
Vol 33 (16) ◽  
pp. 3274-3285 ◽  
Author(s):  
Caroline J. Woo ◽  
Peter V. Kharchenko ◽  
Laurence Daheron ◽  
Peter J. Park ◽  
Robert E. Kingston
Keyword(s):  
Dna Binding ◽  
Cell Fate ◽  
Binding Proteins ◽  
Regulatory Elements ◽  
Dna Binding Proteins ◽  
Polycomb Group ◽  
Content Type ◽  
Evolutionarily Conserved ◽  
Hoxd Cluster ◽  
Hox Clusters

Polycomb group (PcG)-mediated repression is an evolutionarily conserved process critical for cell fate determination and maintenance of gene expression during embryonic development. However, the mechanisms underlying PcG recruitment in mammals remain unclear since few regulatory sites have been identified. We report two novel prospective PcG-dependent regulatory elements within the human HOXB and HOXC clusters and compare their repressive activities to a previously identified element in the HOXD cluster. These regions recruited the PcG proteins BMI1 and SUZ12 to a reporter construct in mesenchymal stem cells and conferred repression that was dependent upon PcG expression. Furthermore, we examined the potential of two DNA-binding proteins, JARID2 and YY1, to regulate PcG activity at these three elements. JARID2 has differential requirements, whereas YY1 appears to be required for repressive activity at all 3 sites. We conclude that distinct elements of the mammalian HOX clusters can recruit components of the PcG complexes and confer repression, similar to what has been seen inDrosophila. These elements, however, have diverse requirements for binding factors, which, combined with previous data on other loci, speaks to the complexity of PcG targeting in mammals.

scholarly journals Defective satellite DNA clustering into chromocenters underlies hybrid incompatibility in Drosophila

2021 ◽  
Author(s):  
Madhav Jagannathan ◽  
Yukiko M Yamashita
Keyword(s):  
Satellite Dna ◽  
Rapid Evolution ◽  
Dna Binding Proteins ◽  
Dna Repeats ◽  
Hybrid Cells ◽  
Entire Genome ◽  
Closely Related Species ◽  
Hybrid Incompatibility ◽  
Cluster Satellite ◽  
Single Nucleus

Although rapid evolution of pericentromeric satellite DNA repeats is theorized to promote hybrid incompatibility (HI), how divergent repeats affect hybrid cells remains poorly understood. Recently, we demonstrated that sequence-specific DNA-binding proteins cluster satellite DNA from multiple chromosomes into chromocenters, thereby bundling chromosomes to maintain the entire genome in a single nucleus. Here we show that ineffective clustering of divergent satellite DNA in the cells of Drosophila hybrids results in chromocenter disruption, associated micronuclei formation and tissue atrophy. We further demonstrate that previously identified HI factors trigger chromocenter disruption and micronuclei in hybrids, linking their function to a conserved cellular process. Together, we propose a unifying framework that explains how the widely observed satellite DNA divergence between closely related species can cause reproductive isolation.

scholarly journals Non-B-form DNA structures mark centromeres

2017 ◽  
Author(s):  
Sivakanthan Kasinathan ◽  
Steven Henikoff
Keyword(s):  
Dna Binding ◽  
Satellite Dna ◽  
Binding Sites ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Genetic Characteristics ◽  
Dna Structures ◽  
Centromere Function ◽  
General Basis ◽  
Human And Mouse

AbstractAnimal and plant centromeres are embedded in repetitive “satellite” DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA binding proteins with DNA bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically non-essential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. Our findings resolve the CENP-B paradox and provide a general basis for centromere specification.

scholarly journals Non-B-Form DNA Is Enriched at Centromeres

2018 ◽  
Vol 35 (4) ◽  
pp. 949-962 ◽  
Author(s):  
Sivakanthan Kasinathan ◽  
Steven Henikoff
Keyword(s):  
Dna Binding ◽  
Satellite Dna ◽  
Binding Sites ◽  
Binding Proteins ◽  
Dna Binding Proteins ◽  
Genetic Characteristics ◽  
Dna Structures ◽  
Centromere Function ◽  
General Basis ◽  
Human And Mouse

AbstractAnimal and plant centromeres are embedded in repetitive “satellite” DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA-binding proteins with DNA-bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B-form DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically nonessential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. This may resolve the CENP-B paradox and provide a general basis for centromere specification.

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