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  1. Article ; Online: Epigenetic profiling reveals key genes and cis-regulatory networks specific to human parathyroids.

    Jung, Youngsook Lucy / Zhao, Wenping / Li, Ian / Jain, Dhawal / Epstein, Charles B / Bernstein, Bradley E / Parangi, Sareh / Sherwood, Richard / Robinson-Cohen, Cassianne / Hsu, Yi-Hsiang / Park, Peter J / Mannstadt, Michael

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 2106

    Abstract: In all terrestrial vertebrates, the parathyroid glands are critical regulators of calcium homeostasis and the sole source of parathyroid hormone (PTH). Hyperparathyroidism and hypoparathyroidism are clinically important disorders affecting multiple ... ...

    Abstract In all terrestrial vertebrates, the parathyroid glands are critical regulators of calcium homeostasis and the sole source of parathyroid hormone (PTH). Hyperparathyroidism and hypoparathyroidism are clinically important disorders affecting multiple organs. However, our knowledge regarding regulatory mechanisms governing the parathyroids has remained limited. Here, we present the comprehensive maps of the chromatin landscape of the human parathyroid glands, identifying active regulatory elements and chromatin interactions. These data allow us to define regulatory circuits and previously unidentified genes that play crucial roles in parathyroid biology. We experimentally validate candidate parathyroid-specific enhancers and demonstrate their integration with GWAS SNPs for parathyroid-related diseases and traits. For instance, we observe reduced activity of a parathyroid-specific enhancer of the Calcium Sensing Receptor gene, which contains a risk allele associated with higher PTH levels compared to the wildtype allele. Our datasets provide a valuable resource for unraveling the mechanisms governing parathyroid gland regulation in health and disease.
    MeSH term(s) Animals ; Humans ; Calcium/metabolism ; Parathyroid Glands/metabolism ; Parathyroid Hormone/genetics ; Parathyroid Hormone/metabolism ; Chromatin/genetics ; Epigenesis, Genetic
    Chemical Substances Calcium (SY7Q814VUP) ; Parathyroid Hormone ; Chromatin
    Language English
    Publishing date 2024-03-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-46181-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: ERα-associated translocations underlie oncogene amplifications in breast cancer.

    Lee, Jake June-Koo / Jung, Youngsook Lucy / Cheong, Taek-Chin / Espejo Valle-Inclan, Jose / Chu, Chong / Gulhan, Doga C / Ljungström, Viktor / Jin, Hu / Viswanadham, Vinayak V / Watson, Emma V / Cortés-Ciriano, Isidro / Elledge, Stephen J / Chiarle, Roberto / Pellman, David / Park, Peter J

    Nature

    2023  Volume 618, Issue 7967, Page(s) 1024–1032

    Abstract: Focal copy-number amplification is an oncogenic event. Although recent studies have revealed the complex ... ...

    Abstract Focal copy-number amplification is an oncogenic event. Although recent studies have revealed the complex structure
    MeSH term(s) Female ; Humans ; Breast Neoplasms/genetics ; Estrogen Receptor alpha/metabolism ; Estrogens/metabolism ; Gene Amplification ; Oncogenes/genetics ; Translocation, Genetic/genetics ; Genome, Human/genetics ; DNA Breaks, Double-Stranded ; Organ Specificity
    Chemical Substances Estrogen Receptor alpha ; Estrogens ; ESR1 protein, human ; ERBB2 protein, human (EC 2.7.10.1) ; CCND1 protein, human
    Language English
    Publishing date 2023-05-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06057-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 26: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

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  3. Article ; Online: Sex comb on midleg (Scm) is a functional link between PcG-repressive complexes in Drosophila.

    Kang, Hyuckjoon / McElroy, Kyle A / Jung, Youngsook Lucy / Alekseyenko, Artyom A / Zee, Barry M / Park, Peter J / Kuroda, Mitzi I

    Genes & development

    2015  Volume 29, Issue 11, Page(s) 1136–1150

    Abstract: The Polycomb group (PcG) proteins are key regulators of development in Drosophila and are strongly implicated in human health and disease. How PcG complexes form repressive chromatin domains remains unclear. Using cross-linked affinity purifications of ... ...

    Abstract The Polycomb group (PcG) proteins are key regulators of development in Drosophila and are strongly implicated in human health and disease. How PcG complexes form repressive chromatin domains remains unclear. Using cross-linked affinity purifications of BioTAP-Polycomb (Pc) or BioTAP-Enhancer of zeste [E(z)], we captured all PcG-repressive complex 1 (PRC1) or PRC2 core components and Sex comb on midleg (Scm) as the only protein strongly enriched with both complexes. Although previously not linked to PRC2, we confirmed direct binding of Scm and PRC2 using recombinant protein expression and colocalization of Scm with PRC1, PRC2, and H3K27me3 in embryos and cultured cells using ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing). Furthermore, we found that RNAi knockdown of Scm and overexpression of the dominant-negative Scm-SAM (sterile α motif) domain both affected the binding pattern of E(z) on polytene chromosomes. Aberrant localization of the Scm-SAM domain in long contiguous regions on polytene chromosomes revealed its independent ability to spread on chromatin, consistent with its previously described ability to oligomerize in vitro. Pull-downs of BioTAP-Scm captured PRC1 and PRC2 and additional repressive complexes, including PhoRC, LINT, and CtBP. We propose that Scm is a key mediator connecting PRC1, PRC2, and transcriptional silencing. Combined with previous structural and genetic analyses, our results strongly suggest that Scm coordinates PcG complexes and polymerizes to produce broad domains of PcG silencing.
    MeSH term(s) Animals ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Histones/metabolism ; Polycomb-Group Proteins/genetics ; Polycomb-Group Proteins/metabolism ; Polytene Chromosomes/metabolism ; Protein Binding ; Protein Transport ; Repressor Proteins/metabolism
    Chemical Substances Drosophila Proteins ; Histones ; Polycomb-Group Proteins ; Repressor Proteins ; SCM protein, Drosophila
    Language English
    Publishing date 2015-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 806684-x
    ISSN 1549-5477 ; 0890-9369
    ISSN (online) 1549-5477
    ISSN 0890-9369
    DOI 10.1101/gad.260562.115
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2292: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 54: Show issues

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