scholarly journals Faculty Opinions recommendation of Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization.

2018 ◽  
Author(s):  
Rolf Ohlsson ◽  
Anita Gondor
Keyword(s):  
Chromosome Domains ◽  
Local Insulation

scholarly journals Targeted degradation of CTCF decouples local insulation of chromosome domains from higher-order genomic compartmentalization

2016 ◽  
Author(s):  
Elphege P Nora ◽  
Anton Goloborodko ◽  
Anne-Laure Valton ◽  
Johan Harmen Gibcus ◽  
Alec Uebersohn ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Chromosomal Structure ◽  
Insulator Function ◽  
Chromosome Domains ◽  
Dividing Cells ◽  
Chromatin Folding ◽  
Enhancer Blocking ◽  
Local Insulation ◽  
Candidate Regulator

The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and segmental organization into topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding, and CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Further, our data supports that CTCF mediates transcriptional insulator function through enhancer-blocking but not direct chromatin barrier activity. These results define the functions of CTCF in chromosome folding, and provide new fundamental insights into the rules governing mammalian genome organization.

scholarly journals Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization

Cell ◽  
2017 ◽  
Vol 169 (5) ◽  
pp. 930-944.e22 ◽  
Author(s):  
Elphège P. Nora ◽  
Anton Goloborodko ◽  
Anne-Laure Valton ◽  
Johan H. Gibcus ◽  
Alec Uebersohn ◽  
...  
Keyword(s):  
Chromosome Domains ◽  
Local Insulation

scholarly journals Phosphorylation of the synaptonemal complex protein SYP-1 promotes meiotic chromosome segregation

2017 ◽  
Author(s):  
Aya Sato-Carlton ◽  
Chihiro Nakamura-Tabuchi ◽  
Stephane Kazuki Chartrand ◽  
Tomoki Uchino ◽  
Peter Mark Carlton
Keyword(s):  
Synaptonemal Complex ◽  
Meiotic Chromosome ◽  
C Elegans ◽  
Chromosome Domains ◽  
Chromatid Cohesion ◽  
Complex Protein ◽  
Chromosomal Passenger ◽  
Synaptonemal Complex Protein ◽  
A Site ◽  
Meiosis I

AbstractChromosomes that have undergone crossing-over in meiotic prophase must maintain sister chromatid cohesion somewhere along their length between the first and second meiotic divisions. While many eukaryotes use the centromere as a site to maintain cohesion, the holocentric organism C. elegans instead creates two chromosome domains of unequal length termed the short arm and long arm, which become the first and second site of cohesion loss at meiosis I and II. The mechanisms that confer distinct functions to the short and long arm domains remain poorly understood. Here, we show that phosphorylation of the synaptonemal complex protein SYP-1 is required to create these domains. Once crossovers are made, phosphorylated SYP-1 and PLK-2 become cooperatively confined to short arms and guide phosphorylated histone H3 and the chromosomal passenger complex to the site of meiosis I cohesion loss. Our results show that PLK-2 and phosphorylated SYP-1 ensure creation of the short arm subdomain, promoting disjunction of chromosomes in meiosis I.

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

2021 ◽  
Author(s):  
Caitlin Connolly ◽  
Saori Takahashi ◽  
Hisashi Miura ◽  
Ichiro Hiratani ◽  
Nick Gilbert ◽  
...  
Keyword(s):  
Dna Replication ◽  
Biological Activities ◽  
Timing Analysis ◽  
Replication Timing ◽  
Synthesis Rate ◽  
Open Chromatin ◽  
Replication Fork Progression ◽  
Chromosome Domains ◽  
Origin Licensing ◽  
In Cells

The organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold attachment factor A (SAF-A), also known as Heteronuclear Ribonucleoprotein Protein U (HNRNPU), contributes to the formation of open chromatin structure. Here we demonstrate that SAF-A promotes the normal progression of DNA replication, and enables resumption of replication after inhibition. We report that cells depleted for SAF-A show reduced origin licensing in G1 phase, and consequently reduced origin activation frequency in S phase. Replication forks progress slowly in cells depleted for SAF-A, also contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed that the boundaries between early- and late- replicating domains are blurred in cells depleted for SAF-A. Associated with these defects, SAF-A-depleted cells show elevated gH2A phosphorylation and tend to enter quiescence. Overall we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.

Detection of barley chromatin added to wheat by genomic in situ hybridization

Genome ◽  
1991 ◽  
Vol 34 (3) ◽  
pp. 448-452 ◽  
Author(s):  
Y. Mukai ◽  
B. S. Gill
Keyword(s):  
In Situ Hybridization ◽  
Genomic Dna ◽  
Repeat Sequence ◽  
Genomic Clone ◽  
Genomic In Situ Hybridization ◽  
Addition Lines ◽  
Interphase Nuclei ◽  
Nucleolar Organizing Region ◽  
Chromosome Domains

A technique for in situ hybridization is reported that can be used to detect barley chromatin in wheat background using total genomic DNA as a probe. A 1:2 ratio of biotin-labeled genomic DNA of barley to blocking (unlabeled, sheared) DNA of wheat was sufficient to reveal brownish labeled barley chromosome domains against bluish background of unlabeled wheat chromatin in metaphase, prophase, and interphase nuclei of wheat-barley addition lines. Using this procedure, the behavior of specific barley chromosomes was analyzed in interphase and prophase cells. In prophase cells, the 6H chromosome was always associated with a nucleolus. A genomic clone of α-amylase gene (gRAmy56) that contains a barley-specific dispersed repeat sequence was also used to detect barley chromosomes in a wheat background.Key words: Hordeum vulgare, Triticum aestivum, genomic in situ hybridization, biotin, nucleolar organizing region.

scholarly journals Decoding the centromeric nucleosome through CENP-N

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Satyakrishna Pentakota ◽  
Keda Zhou ◽  
Charlotte Smith ◽  
Stefano Maffini ◽  
Arsen Petrovic ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Double Helix ◽  
Structural Basis ◽  
Binding Motif ◽  
Kinetochore Assembly ◽  
Nucleosomal Dna ◽  
Chromosome Domains ◽  
Histone H3 Variant ◽  
Spindle Microtubules ◽  
Dna Double Helix

Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.

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