Mislocalization of the Centromeric Histone Variant CenH3/CENP-A in Human Cells Depends on the Chaperone DAXX

Lacoste, Nicolas; Woolfe, Adam; Tachiwana, Hiroaki; Villar-Garea, Ana; Barth, Teresa K.; Cantaloube, Sylvain; Kurumizaka, Hitoshi; Imhof, Axel; Almouzni, Geneviève

doi:10.1016/j.molcel.2014.01.018

Cited by 215 publications

(338 citation statements)

References 54 publications

Supporting

Mentioning

309

Contrasting

Order By: Relevance

“…The sensitivity of the uncross-linked CCAN to MNase digestion can account in part for the differences in DNA protection that led to conflicting conclusions about the structure of the CENP-A nucleosome. However, by following N-ChIP with salt fractionation, we now show that CENP-A particles observed using low-salt conditions (Lacoste et al 2014;Nechemia-Arbely et al 2017) comprise only a minor fraction of the total CENP-A genome-wide. In contrast, the major N-ChIP salt fraction consists of particles that protect much larger DNA fragments, consistent with the presence of an intact CCAN complex.…”

Section: Divergent α Satellites Retain Some Competence For Cenp-a Assmentioning

confidence: 78%

“…We wondered whether the relative lack of large fragments obtained using N-ChIP in other published studies (Lacoste et al 2014;Henikoff et al 2015;Nechemia-Arbely et al 2017) might have resulted from the failure to solubilize most centromeric chromatin under low-salt conditions. To address this possibility, we prepared Illumina sequencing libraries from N-ChIP salt fractions and subjected them to paired-end sequencing.…”

Section: Ccan Complexes Extracted With High Salt Are Heterogeneous Inmentioning

confidence: 99%

See 1 more Smart Citation

Unexpected conformational variations of the human centromeric chromatin complex

Thakur

Henikoff

2018

Genes Dev.

View full text Add to dashboard Cite

We combined classical salt fractionation with chromatin immunoprecipitation to recover human centromeric chromatin under native conditions. We found that >85% of the total centromeric chromatin is insoluble under conditions typically used for native chromatin extraction. To map both soluble and insoluble chromatin in situ, we combined CUT&RUN (cleavage under targets and release using nuclease), a targeted nuclease method, with salt fractionation. Using this approach, we observed unexpected structural and conformational variations of centromere protein A (CENP-A)-containing complexes on different α-satellite dimeric units within highly homogenous arrays. Our results suggest that slight α-satellite sequence differences control the structure and occupancy of the associated centromeric chromatin complex.

show abstract

Section: Divergent α Satellites Retain Some Competence For Cenp-a Assmentioning

confidence: 78%

Section: Ccan Complexes Extracted With High Salt Are Heterogeneous Inmentioning

confidence: 99%

Unexpected conformational variations of the human centromeric chromatin complex

Thakur

Henikoff

2018

Genes Dev.

View full text Add to dashboard Cite

show abstract

“…Ordinarily, CENH3 is enriched at the positions of the centromeres but can also be present to some degree elsewhere on the chromosome (40). However, the incorporation into arms is a regular occurrence upon overexpression of CENH3 (41,42), which can produce ectopic centromeres, suggesting that a continuum of frequency of de novo centromere formation might exist. Under normal conditions, one possibility might be that any de novo centromere formation is blocked in the arms.…”

Section: Discussionmentioning

confidence: 99%

Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize

Liu

Pang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The ability of centromeres to alternate between active and inactive states indicates significant epigenetic aspects controlling centromere assembly and function. In maize (Zea mays), misdivision of the B chromosome centromere on a translocation with the short arm of chromosome 9 (TB-9Sb) can produce many variants with varying centromere sizes and centromeric DNA sequences. In such derivatives of TB-9Sb, we found a de novo centromere on chromosome derivative 3-3, which has no canonical centromeric repeat sequences. This centromere is derived from a 288-kb region on the short arm of chromosome 9, and is 19 megabases (Mb) removed from the translocation breakpoint of chromosome 9 in TB-9Sb. The functional B centromere in progenitor telo2-2 is deleted from derivative 3-3, but some B-repeat sequences remain. The de novo centromere of derivative 3-3 becomes inactive in three further derivatives with new centromeres being formed elsewhere on each chromosome. Our results suggest that de novo centromere initiation is quite common and can persist on chromosomal fragments without a canonical centromere. However, we hypothesize that when de novo centromeres are initiated in opposition to a larger normal centromere, they are cleared from the chromosome by inactivation, thus maintaining karyotype integrity.centromere misdivision | epigenetics | de novo centromere | centromere inactivation T he centromere is an important chromosomal region responsible for correct chromosome segregation during cell division. Centromeres are found in the primary constriction region on the chromosome, upon which the kinetochore complex assembles to produce a platform for spindle binding (1). Centromere function is conserved among different species, and several epigenetic markers of active centromeres have been found, including a histone H3 variant referred to as CENH3 in plants (2, 3) or CENP-A in animals (4-6) and phosphorylation of histone H2A at Thr133 in plants (7). Correct loading of CENH3 to the centromere region is a key component of kinetochore assembly (8). Centromeric DNA sequences have experienced rapid evolution (9, 10), and arrangements of DNA sequence in centromere regions differ in species and even in different chromosomes of an individual organism (11). Myriad repeat sequences exist in the centromeres of higher plants. In maize (Zea mays), there are two major types of centromere specific DNA sequences: the simple satellite repeat sequence CentC (12) and centromeric retrotransposon of maize (CRM) (3). Many epigenetic features have been identified in centromeric regions, including DNA methylation levels, histone variants, histone modifications, and RNA components (11). Both epigenetic elements and DNA sequences take part in centromere formation and maintenance, but it is still unknown how genetic and epigenetic factors work together in this process.The centromere is one of the most complex regions on the chromosome, and complete DNA sequencing through the centromeric region is difficult to obtain due to their highly repetitive nature...

show abstract

“…In fact, histone chaperones have emerged as key players in the transient disorganization of chromatin required in the DNA repair process. Thus, the histone chaperones aprataxin-PNK-like factor (APLF) (6), antisilencing function 1 (Asf1) (9), chromatin assembly factor 1 (CAF-1) (10), death domain-associated protein 6 (DAXX) (11), facilitating chromatin transcription (FACT) (12), histone regulator A (HIRA) (13), nucleolin (14), p400 (15), and nucleosome assembly protein 1-like 1 (NAP1L1) and 1-like 4 (NAP1L4) (7) are recruited to damaged chromatin, thereby promoting histone dynamics in response to DNA damage. Recently, SET/TAF-1β was found to be recruited to DNA breaks to modulate the DNA damage response through the retention of certain chromatin proteins, resulting in chromatin compaction (16).…”

mentioning

confidence: 99%

Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c

González‐Arzola

Dı́az-Moreno

Cano-González

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

114

View full text Add to dashboard Cite

Chromatin is pivotal for regulation of the DNA damage process insofar as it influences access to DNA and serves as a DNA repair docking site. Recent works identify histone chaperones as key regulators of damaged chromatin’s transcriptional activity. However, understanding how chaperones are modulated during DNA damage response is still challenging. This study reveals that the histone chaperone SET/TAF-Iβ interacts with cytochrome c following DNA damage. Specifically, cytochrome c is shown to be translocated into cell nuclei upon induction of DNA damage, but not upon stimulation of the death receptor or stress-induced pathways. Cytochrome c was found to competitively hinder binding of SET/TAF-Iβ to core histones, thereby locking its histone-binding domains and inhibiting its nucleosome assembly activity. In addition, we have used NMR spectroscopy, calorimetry, mutagenesis, and molecular docking to provide an insight into the structural features of the formation of the complex between cytochrome c and SET/TAF-Iβ. Overall, these findings establish a framework for understanding the molecular basis of cytochrome c-mediated blocking of SET/TAF-Iβ, which subsequently may facilitate the development of new drugs to silence the oncogenic effect of SET/TAF-Iβ’s histone chaperone activity.

show abstract

Mislocalization of the Centromeric Histone Variant CenH3/CENP-A in Human Cells Depends on the Chaperone DAXX

Cited by 215 publications

References 54 publications

Unexpected conformational variations of the human centromeric chromatin complex

Unexpected conformational variations of the human centromeric chromatin complex

Sequential de novo centromere formation and inactivation on a chromosomal fragment in maize

Structural basis for inhibition of the histone chaperone activity of SET/TAF-Iβ by cytochrome c

Contact Info

Product

Resources

About