Epigenetic patterns in a complete human genome Gershman, Ariel; Sauria, Michael E G; Guitart, Xavi ...
Science (American Association for the Advancement of Science),
04/2022, Volume:
376, Issue:
6588
Journal Article
Peer reviewed
Open access
The completion of a telomere-to-telomere human reference genome, T2T-CHM13, has resolved complex regions of the genome, including repetitive and homologous regions. Here, we present a high-resolution ...epigenetic study of previously unresolved sequences, representing entire acrocentric chromosome short arms, gene family expansions, and a diverse collection of repeat classes. This resource precisely maps CpG methylation (32.28 million CpGs), DNA accessibility, and short-read datasets (166,058 previously unresolved chromatin immunoprecipitation sequencing peaks) to provide evidence of activity across previously unidentified or corrected genes and reveals clinically relevant paralog-specific regulation. Probing CpG methylation across human centromeres from six diverse individuals generated an estimate of variability in kinetochore localization. This analysis provides a framework with which to investigate the most elusive regions of the human genome, granting insights into epigenetic regulation.
Aurora B kinase phosphorylates kinetochore proteins during early mitosis, increasing kinetochore–microtubule (MT) turnover and preventing premature stabilization of kinetochore–MT attachments. ...Phosphorylation of kinetochore proteins during late mitosis is low, promoting attachment stabilization, which is required for anaphase onset. The kinetochore protein KNL1 recruits Aurora B–counteracting phosphatases and the Aurora B–targeting factor Bub1, yet the consequences of KNL1 depletion on Aurora B phospho-regulation remain unknown. Here, we demonstrate that the KNL1 N terminus is essential for Aurora B activity at kinetochores. This region of KNL1 is also required for Bub1 kinase activity at kinetochores, suggesting that KNL1 promotes Aurora B activity through Bub1-mediated Aurora B targeting. However, ectopic targeting of Aurora B to kinetochores does not fully rescue Aurora B activity in KNL1-depleted cells, suggesting KNL1 influences Aurora B activity through an additional pathway. Our findings establish KNL1 as a requirement for Aurora B activity at kinetochores and for wild-type kinetochore–MT attachment dynamics.
The spindle assembly checkpoint is a surveillance mechanism that blocks anaphase onset until all chromosomes are properly attached to microtubules of the mitotic spindle. Checkpoint activity requires ...kinetochore localization of Mad1/Mad2 to inhibit activation of the anaphase promoting complex/cyclosome in the presence of unattached kinetochores. In budding yeast and Caenorhabditis elegans, Bub1, recruited to kinetochores through KNL1, recruits Mad1/Mad2 by direct linkage with Mad1. However, in human cells it is not yet established which kinetochore protein(s) function as the Mad1/Mad2 receptor. Both Bub1 and the RZZ complex have been implicated in Mad1/Mad2 kinetochore recruitment; however, their specific roles remain unclear. Here, we investigate the contributions of Bub1, RZZ and KNL1 to Mad1/Mad2 kinetochore recruitment. We find that the RZZ complex localizes to the N-terminus of KNL1, downstream of Bub1, to mediate robust Mad1/Mad2 kinetochore localization. Our data also point to the existence of a KNL1-, Bub1-independent mechanism for RZZ and Mad1/Mad2 kinetochore recruitment. Based on our results, we propose that in humans, the primary mediator for Mad1/Mad2 kinetochore localization is the RZZ complex.
ABSTRACT
Iron and zinc are essential micronutrients for human health often found in insufficient quantities in the diet. Biofortification of seed crops has been undertaken to reduce micronutrient ...malnutrition. The objectives of this study were to identify variability for seed Fe, Zn, P, and phytic acid levels in an F5:7 recombinant inbred line (RIL) population developed from a cross between AND696 and G19833, both common beans (Phaseolus vulgaris L.) of Andean origin. Quantitative trait loci (QTL) analysis was conducted with data from 2 yr and 2 P treatments with a previously described linkage map of AND696/G19833. Significant environmental and genetic variability for Fe, Zn, and P levels was identified, and Fe and Zn levels were correlated (up to r=0.53). Quantitative trait loci for seed Fe and Zn co‐localized on three linkage groups (B1, B6, and B11). On B6, a QTL for Fe (R2 = 0.36) was found at the same marker interval as a QTL for seed Zn (R2 = 0.39), both derived from AND696. Quantitative trait loci for seed P were identified on six linkage groups and explained 17 to 55% of the total phenotypic variation depending on year and environment.
KNL1 is an evolutionarily conserved kinetochore-associated protein essential for accurate chromosome segregation in eukaryotic cells. This large scaffold protein, predicted to be almost entirely ...unstructured, is involved in diverse mitotic processes including kinetochore assembly, chromosome congression, and mitotic checkpoint signaling. How this kinetochore “hub” coordinates protein–protein interactions spatially and temporally during mitosis to orchestrate these processes is an area of active investigation. Here we summarize the current understanding of KNL1 and discuss possible mechanisms by which this protein actively contributes to multiple aspects of mitotic progression.
In this issue of Molecular Cell, Han et al. (2013) demonstrate that Mad2 induces a conformational change in Cdc20 that permits BubR1 binding, thereby producing the physiologically relevant APC/CCdc20 ...inhibitor.
Seed coat colour in common bean(Phaseolus vulgaris L.) is determined by activity of the flavonoid biosynthetic pathway resulting in the presence or absence of specific anthocyanins, tannins and ...glycosidic flavanols. These secondary metabolites have anti-oxidant properties in the case of anthocyanins and glycosidic flavonols and strongly influence dietary mineral bioavailability in the case of tannins. The modification of tannin content is a goal of biofortification breeding programs, while almost all bean improvement considers seed colour in selection priorities as this affects consumer preference and food quality. In the present study, we analyzed condensed tannins, tannin monomers and anthocyanin levels in an inter-genepool population derived from the cross DOR364 x G19833 using HPLC and spectrophotometric methods. The overall average for condensed tannins expressed as percentage in seed coats was 20.04%. The ranges were between 8.0% and 27.9% for soluble tannins (ST), 1.5% and 5.4% for insoluble tannins (IT), and 10.7% and 30.9% for total tannins (TT). Anthocyanins in seed coats averaged 0.08% (0.013-0.21% range) expressed as delphinidin-3-glucoside equivalents for the population with the distribution biased towards low content. All traits had large variability between genotypes and showed transgressive segregation, indicating quantitative inheritance for tannin content and oligogenic control of anthocyanins. Condensed tannins in the genotypes were mainly composed of catechin (60.3%), gallocatechin (25%), and afzelechin (14.7%) as monomeric units.
Complete genomic and epigenetic maps of human centromeres Altemose, Nicolas; Logsdon, Glennis A; Bzikadze, Andrey V ...
Science (American Association for the Advancement of Science),
04/2022, Volume:
376, Issue:
6588
Journal Article
Peer reviewed
Open access
Existing human genome assemblies have almost entirely excluded repetitive sequences within and near centromeres, limiting our understanding of their organization, evolution, and functions, which ...include facilitating proper chromosome segregation. Now, a complete, telomere-to-telomere human genome assembly (T2T-CHM13) has enabled us to comprehensively characterize pericentromeric and centromeric repeats, which constitute 6.2% of the genome (189.9 megabases). Detailed maps of these regions revealed multimegabase structural rearrangements, including in active centromeric repeat arrays. Analysis of centromere-associated sequences uncovered a strong relationship between the position of the centromere and the evolution of the surrounding DNA through layered repeat expansions. Furthermore, comparisons of chromosome X centromeres across a diverse panel of individuals illuminated high degrees of structural, epigenetic, and sequence variation in these complex and rapidly evolving regions.
The color of the seed coats of ‘Dorado’ (
Phaseolus vulgaris
L.) is garnet brown (dark red kidney bean color) and differs from most other dry bean varieties in the Honduran red bean market class. A ...genetic investigation of the color of ‘Dorado’ (same as DOR364) and G19833 (Liborino market class) seed coats was conducted. Crosses with genetic tester stocks demonstrated that the gene for garnet brown (GB) in ‘Dorado’ was not allelic with the
R
gene for dominant red (oxblood) seed coat. An allelism test between the ‘Dorado’ gene for GB seed coat and the
rk
drv
gene for recessive expression of GB demonstrated allelism. We propose the gene symbol for
Rk
r
for the ‘Dorado’ GB seed coat color gene.
Rk
r
expresses partial dominance over
Rk
, where
Rk
r
/
Rk
expresses a paler and highly variable intermediate red color. The interactions of
Rk
r
,
rk
drv
, and
c
u
are discussed. Segregation analysis in the mapping population made up of DOR364 (same as ‘Dorado’) × G19833 recombinant inbred lines showed that the
Rk
r
gene mapped to linkage group 1. The new allele at
Rk
was located at a distance of 17 cM from the RFLP marker Bng130 with a LOD > 3.0.
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