Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches

Prosun Das, Kylee J. Veazey, Hieu T. Van, Saakshi Kaushik, Kevin Lin, Yue Lu, Masaru Ishii, Junichi Kikuta, Kai Ge, Andre Nussenzweig, Margarida A. Santos

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The bone is essential for locomotion, calcium storage, and harboring the hematopoietic stem cells (HSCs) that supply the body with mature blood cells throughout life. HSCs reside at the interface of the bone and bone marrow (BM), where active bone remodeling takes place. Although the cellular components of the BM niche have been characterized, little is known about its epigenetic regulation. Here we find that the histone methylation regulator PTIP (Pax interaction with transcription-activation domain protein-1) is required to maintain the integrity of the BM niche by promoting osteoclast differentiation. PTIP directly promotes chromatin changes required for the expression of PPAR? (peroxisome proliferator-activated receptor-?), a transcription factor essential for osteoclastogenesis. PTIP deletion leads to a drastic reduction of HSCs in the BM and induces extramedullary hematopoiesis. Furthermore, exposure of acute myeloid leukemia cells to a PTIP-deficient BM microenvironment leads to a reduction in leukemia-initiating cells and increased survival upon transplantation. Taken together, our data identify PTIP as an epigenetic regulator of osteoclastogenesis that is required for the integrity of the BM niche to sustain both normal hematopoiesis and leukemia.

Original languageEnglish (US)
Pages (from-to)E10137-E10146
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number43
DOIs
StatePublished - Oct 23 2018

Keywords

  • Epigenetics
  • Hematopoiesis
  • Leukemia
  • Osteoclasts

ASJC Scopus subject areas

  • General

MD Anderson CCSG core facilities

  • Science Park Flow Cytometry

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