HIRA orchestrates a non-canonical dynamic chromatin landscape in senescence and is required for suppression of neoplasia

Taranjit Singh Rai, John C. Cole, David M. Nelson, Dina Dikovskaya, Tony McBryan, William Faller, John v. Tuyn, Nicholas Morrice, Rachael N. Hewitt, Claire Brock, Andrejs Ivanov, Mark E. Drotar, Colin Nixon, William Clark, Owen J. Sansom, Ayala King, Karen Blyth, Peter D. Adams

    Research output: Contribution to conferencePoster

    Abstract

    Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cell senescence and associated tumor suppression depend on control of chromatin. Chromatin is dynamically controlled, and its imbalance can promote cancer, as evidenced by recurrent mutations and dysregulation in cancer of H3.3, a histone variant enriched at dynamic chromatin regulatory sites. Hence, it is important to understand the impact of dynamic chromatin control on tumor suppression. We show that non-proliferating tumor suppressive senescent cells express and incorporate histone H3.3 and normally "replication-dependent" histones into a non-canonical, H4K16ac-decorated, dynamic chromatin landscape. A key regulator of this landscape, histone chaperone HIRA, is required for suppression of oncogene-induced neoplasia in vivo. These results indicate a role for a non-canonical, dynamic chromatin landscape in tumor suppression.
    Original languageEnglish
    Publication statusPublished - 9 Sep 2014
    EventEpigenetics & Chromatin CSHL 2014: Cold Spring Harbor Laboratory Meeting on Epigenetics & Chromatin - Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Duration: 9 Sep 201413 Sep 2014
    http://epigenie.com/conferences/epigenetics-chromatin-cshl-2014/ (Notice of meeting)

    Conference

    ConferenceEpigenetics & Chromatin CSHL 2014
    Country/TerritoryUnited States
    CityCold Spring Harbor
    Period9/09/1413/09/14
    Internet address

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