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早幼粒细胞白血病蛋白（PML）是染色质结构域的一个组成成分，在癌细胞中富含重复元件和重复基因簇。

PML is a constitutive component of chromatin domains enriched in repetitive elements and duplicated gene clusters in cancer cells.

作者信息

Fracassi Cristina, Simoni Matilde, Uggè Martina, Morelli Marco J, Bernardi Rosa

机构信息

Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milano, Italy.

Center for Omics Sciences, IRCCS San Raffaele Scientific Institute, Milano, Italy.

出版信息

Heliyon. 2024 Aug 17;10(17):e36499. doi: 10.1016/j.heliyon.2024.e36499. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e36499
PMID:39263139
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11387257/
Abstract

Heterochromatin is a pivotal element in the functional organization of genomes. In our study, we delve into the heterochromatin pattern of association by the PML (promyelocytic leukemia) protein. By using PML chromatin immunoprecipitation and sequencing data and comparing computational methodologies to depict PML chromatin association, we describe PML-associated domains or PADs as large heterochromatic regions that exhibit similar genomic features across cancer cell lines. We show that PADs are specifically enriched in non-coding genes, duplicated gene clusters, and repetitive DNA elements. Moreover, we find enriched binding motifs of KZFPs, which are involved in orchestrating epigenetic repression at repetitive DNA elements. Hence, our findings suggest that PML conservatively associates to heterochromatic domains enriched in repetitive DNA elements and duplicated gene clusters in cancer. These findings contribute to a broader understanding of the complex regulatory framework of genome organization by heterochromatin in cancer.

摘要

异染色质是基因组功能组织中的关键要素。在我们的研究中，我们深入探究了早幼粒细胞白血病（PML）蛋白的异染色质关联模式。通过使用PML染色质免疫沉淀和测序数据，并比较用于描绘PML染色质关联的计算方法，我们将PML相关结构域（PADs）描述为在癌细胞系中呈现相似基因组特征的大型异染色质区域。我们表明，PADs在非编码基因、重复基因簇和重复DNA元件中特异性富集。此外，我们发现了锌指蛋白（KZFPs）的富集结合基序，这些基序参与在重复DNA元件处协调表观遗传抑制。因此，我们的研究结果表明，PML在癌症中保守地与富含重复DNA元件和重复基因簇的异染色质结构域相关联。这些发现有助于更广泛地理解癌症中异染色质对基因组组织的复杂调控框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/d0231e1035e8/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/d59c19d212b7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/634aeedbcbec/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/b77a5b78e37a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/1bc904b3c810/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/7be76f3fbed3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/d0231e1035e8/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/d59c19d212b7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/634aeedbcbec/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/b77a5b78e37a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/1bc904b3c810/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/7be76f3fbed3/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ead/11387257/d0231e1035e8/gr6.jpg

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本文引用的文献

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PML restrains p53 activity and cellular senescence in clear cell renal cell carcinoma.PML 抑制透明细胞肾细胞癌中的 p53 活性和细胞衰老。
EMBO Mol Med. 2024 Jun;16(6):1324-1351. doi: 10.1038/s44321-024-00077-3. Epub 2024 May 10.
2
PML Nuclear bodies: the cancer connection and beyond.多系统萎缩小体细胞核包涵体：癌症相关及其他。
Nucleus. 2024 Dec;15(1):2321265. doi: 10.1080/19491034.2024.2321265. Epub 2024 Feb 27.
3
PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer.
PML 通过调节染色质的表观遗传组成来调节三阴性乳腺癌中促转移基因的表达。
Nucleic Acids Res. 2023 Nov 10;51(20):11024-11039. doi: 10.1093/nar/gkad819.
4
PML and PML-like exonucleases restrict retrotransposons in jawed vertebrates.PML 和 PML 样外切核酸酶在有颌脊椎动物中限制逆转录转座子。
Nucleic Acids Res. 2023 Apr 24;51(7):3185-3204. doi: 10.1093/nar/gkad152.
5
Exploration of nuclear body-enhanced sumoylation reveals that PML represses 2-cell features of embryonic stem cells.核体增强的 SUMO 化探索表明，PML 抑制胚胎干细胞的 2 细胞特征。
Nat Commun. 2022 Sep 29;13(1):5726. doi: 10.1038/s41467-022-33147-6.
6
3D genome, on repeat: Higher-order folding principles of the heterochromatinized repetitive genome.三维基因组，再重复：异染色质化重复基因组的高级折叠原则。
Cell. 2022 Jul 21;185(15):2690-2707. doi: 10.1016/j.cell.2022.06.052.
7
PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK.PROX1 通过与 hnRNPK 相互作用，通过 WNT/β-catenin 通路促进乳腺癌的侵袭和转移。
Int J Biol Sci. 2022 Feb 28;18(5):2032-2046. doi: 10.7150/ijbs.68960. eCollection 2022.
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Genome-wide maps of nucleolus interactions reveal distinct layers of repressive chromatin domains.基因组范围内核仁相互作用图谱揭示了不同层次的抑制性染色质域。
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PML nuclear bodies and chromatin dynamics: catch me if you can!PML 核体与染色质动力学：有本事就来抓我呀！
Nucleic Acids Res. 2020 Dec 2;48(21):11890-11912. doi: 10.1093/nar/gkaa828.
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HIF-1α and HIF-2α differently regulate tumour development and inflammation of clear cell renal cell carcinoma in mice.缺氧诱导因子-1α（HIF-1α）和缺氧诱导因子-2α（HIF-2α）在小鼠透明细胞肾细胞癌的肿瘤发生和炎症中发挥不同的作用。
Nat Commun. 2020 Aug 17;11(1):4111. doi: 10.1038/s41467-020-17873-3.