Genome-wide chromatin accessibility is restricted by ANP32E

Murphy, Kristin; Meng, Fanju W.; Makowski, Claire E.; Murphy, Patrick J.

doi:10.1038/s41467-020-18821-x

Cited by 37 publications

(23 citation statements)

References 75 publications

(128 reference statements)

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“…As H2A.Z is incorporated into the same regions of the endogenous H2A.Z in the RhIP assay, the pre-incorporated H2A.Z in the chromatin may be dynamically exchanged with the exogenously added H2A.Z in the RhIP assay. The exchange reaction requires the H2A.Z-H2B complex to be evicted from nucleosomes, and ANP32E has this eviction activity ( Gursoy-Yuzugullu et al, 2015 ; Murphy et al, 2020 ; Murphy et al, 2018 ; Obri et al, 2014 ). We then examined whether ANP32E is involved in the deposition of H2A.Z in the RhIP assay.…”

Section: Resultsmentioning

confidence: 99%

Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay

Tachiwana

Dacher

Maehara

et al. 2021

eLife

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In eukaryotes, histone variant distribution within the genome is the key epigenetic feature. To understand how each histone variant is targeted to the genome, we developed a new method, the RhIP (Reconstituted histone complex Incorporation into chromatin of Permeabilized cell) assay, in which epitope-tagged histone complexes are introduced into permeabilized cells and incorporated into their chromatin. Using this method, we found that H3.1 and H3.3 were incorporated into chromatin in replication-dependent and -independent manners, respectively. We further found that the incorporation of histones H2A and H2A.Z mainly occurred at less condensed chromatin (open), suggesting that condensed chromatin (closed) is a barrier for histone incorporation. To overcome this barrier, H2A, but not H2A.Z, uses a replication-coupled deposition mechanism. Our study revealed that the combination of chromatin structure and DNA replication dictates the differential histone deposition to maintain the epigenetic chromatin states.

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Section: Resultsmentioning

confidence: 99%

Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay

Tachiwana

Dacher

Maehara

et al. 2021

eLife

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“…H2A.Z accumulates at estrogen response elements that are bound by FOXA1 and loss of H2A.Z impairs both FOXA1 binding and polymerase recruitment. ANP32E is a chromatin chaperone that regulates the genomic localization of H2A.Z to control locus-specific chromatin state dynamics [ 14 ]. In recent work, we showed that ANP32E antagonizes H2A.Z installation, such that ANP32E loss causes a global increased H2A.Z enrichment, heightened chromatin accessibility and amplified transcription factor binding at open sites, in cultured mouse fibroblasts [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

“…ANP32E is a chromatin chaperone that regulates the genomic localization of H2A.Z to control locus-specific chromatin state dynamics [ 14 ]. In recent work, we showed that ANP32E antagonizes H2A.Z installation, such that ANP32E loss causes a global increased H2A.Z enrichment, heightened chromatin accessibility and amplified transcription factor binding at open sites, in cultured mouse fibroblasts [ 14 ]. ANP32E may function similarly in breast tumors, influencing the binding of key oncogenic transcription factors, such as FOXA1.…”

Section: Resultsmentioning

confidence: 99%

“…MCF-7 cells were cultured according to methods described previously [ 23 ]. To measure genomic ANP32E enrichment, CUT&Tag experiments were performed as previously described [ 14 , 24 ], using an antibody recognizing ANP32E (Thermo PA5-42860). Libraries were sequenced on Illumina NextSeq550 in 75bp paired-end mode and raw sequencing data was aligned to Hg38 using Bowtie2 [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

“…We recently defined the histone chaperone protein ANP32E as a genome-wide regulator of chromatin accessibility in mouse fibroblasts [ 14 ]. ANP32E functions to modulate the installation/removal of H2A.Z from chromatin, regulating chromatin remodeler activity and limiting chromatin accessibility.…”

Section: Introductionmentioning

confidence: 99%

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Subtype-Independent ANP32E Reduction During Breast Cancer Progression in Accordance with Chromatin Relaxation

et al. 2021

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Background Chromatin state provides a clear decipherable blueprint for maintenance of transcriptional patterns, exemplifying a mitotically stable form of cellular programming in dividing cells. In this regard, genomic studies of chromatin states within cancerous tissues have the potential to uncover novel aspects of tumor biology and unique mechanisms associated with disease phenotypes and outcomes. The degree to which chromatin state differences occur in accordance with breast cancer features has not been established. Methods We applied a series of unsupervised computational methods to identify chromatin and molecular differences associated with discrete physiologies across human breast cancer tumors. Results Chromatin patterns alone are capable of stratifying tumors in association with cancer subtype and disease progression. Major differences occur at DNA motifs for the transcription factor FOXA1, in hormone receptor-positive tumors, and motifs for SOX9 in Basal-like tumors. We find that one potential driver of this effect, the histone chaperone ANP32E, is inversely correlated with tumor progression and relaxation of chromatin at FOXA1 binding sites. Tumors with high levels of ANP32E exhibit an immune response and proliferative gene expression signature, whereas tumors with low ANP32E levels appear programmed for differentiation. Conclusions Our results indicate that ANP32E may function through chromatin state regulation to control breast cancer differentiation and tumor plasticity. This study sets a precedent for future computational studies of chromatin changes in carcinogenesis.

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Hierarchical Accumulation of Histone Variant H2A.Z Regulates Transcriptional States and Histone Modifications in Early Mammalian Embryos

et al. 2022

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Early embryos undergo extensive epigenetic reprogramming to achieve gamete‐to‐embryo transition, which involves the loading and removal of histone variant H2A.Z on chromatin. However, how does H2A.Z regulate gene expression and histone modifications during preimplantation development remains unrevealed. Here, by using ultra‐low‐input native chromatin immunoprecipitation and sequencing, the genome‐wide distribution of H2A.Z is delineated in mouse oocytes and early embryos. These landscapes indicate that paternal H2A.Z is removed upon fertilization, followed by unbiased accumulation on parental genomes during zygotic genome activation (ZGA). Remarkably, H2A.Z exhibits hierarchical accumulation as different peak types at promoters: promoters with double H2A.Z peaks are colocalized with H3K4me3 and indicate transcriptional activation; promoters with a single H2A.Z peak are more likely to occupy bivalent marks (H3K4me3+H3K27me3) and indicate development gene suppression; promoters with no H2A.Z accumulation exhibit persisting gene silencing in early embryos. Moreover, H2A.Z depletion changes the enrichment of histone modifications and RNA polymerase II binding at promoters, resulting in abnormal gene expression and developmental arrest during lineage commitment. Furthermore, similar transcription and accumulation patterns between mouse and porcine embryos indicate that a dual role of H2A.Z in regulating the epigenome required for proper gene expression is conserved during mammalian preimplantation development.

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Genome-wide chromatin accessibility is restricted by ANP32E

Cited by 37 publications

References 75 publications

Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay

Chromatin structure-dependent histone incorporation revealed by a genome-wide deposition assay

Subtype-Independent ANP32E Reduction During Breast Cancer Progression in Accordance with Chromatin Relaxation

Hierarchical Accumulation of Histone Variant H2A.Z Regulates Transcriptional States and Histone Modifications in Early Mammalian Embryos

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