Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

A functional role for the histone demethylase UTX in normal and malignant hematopoietic cells. Exp Hematol 2012 Jun;40(6):487-98.e3

Date

02/07/2012

Pubmed ID

22306297

DOI

10.1016/j.exphem.2012.01.017

Abstract

Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), an H3K27Me2/3 demethylase, has been implicated in development, self-renewal, and differentiation of various organs and embryonic stem cells through chromatin modifications and transcriptional regulation of important developmentally related genes, such as Hox genes. However, the function of UTX in hematopoiesis is not well understood. To study the role of UTX in the mammalian hematopoietic system, we used lentiviral short hairpin RNA constructs to knockdown UTX in the murine hematopoietic progenitor cell line EML, in primary murine bone marrow cells and in leukemic cell lines. We report that Utx is highly expressed in the hematopoietic compartment and that it plays an important role in cell proliferation and homeostasis of hematopoietic cells in vitro. Knockdown of UTX in EML and primary murine bone marrow cells impairs their colony-forming ability. Moreover, knockdown of UTX affects expression of key genes that regulate hematopoietic differentiation such as Mll1, Runx1, and Scl in primary murine bone marrow cells. And we further demonstrate that UTX directly associates with the promoters of the Mll1, Runx1, and Scl genes and modulate their transcription by controlling H3K27me3 marks on respective promoter regions. In addition, UTX depletion severely impaired proliferation of several human leukemia cell lines. Together, these data demonstrate a functional role for UTX in normal and malignant hematopoiesis.

Author List

Liu J, Mercher T, Scholl C, Brumme K, Gilliland DG, Zhu N

Author

Nan Zhu PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Bone Marrow Cells
Cell Line, Tumor
Chromatin Immunoprecipitation
Flow Cytometry
Gene Knockdown Techniques
Hematologic Neoplasms
Hematopoiesis
Histone Demethylases
Humans
Mice
Nuclear Proteins
Real-Time Polymerase Chain Reaction
Transcription, Genetic
jenkins-FCD Prod-403 0f9a74600e4e79798f8fa6f545ea115f3dd948b2