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J Mol Biol. 2017 Jun 30;429(13):2093-2107. doi: 10.1016/j.jmb.2016.10.026. Epub 2016 Oct 27.

Myeloid Leukemia Factor Acts in a Chaperone Complex to Regulate Transcription Factor Stability and Gene Expression.

Author information

1
Department of Biology, Rockhurst University, Kansas City, MO 64110, USA.
2
Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA.
3
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
4
Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
5
Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
6
Stowers Institute for Medical Research, Kansas City, MO 64110, USA; Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA. Electronic address: sma@stowers.org.
7
Stowers Institute for Medical Research, Kansas City, MO 64110, USA. Electronic address: jlw@stowers.org.

Abstract

Mutations that affect myelodysplasia/myeloid leukemia factor (MLF) proteins are associated with leukemia and several other cancers. However, with no strong homology to other proteins of known function, the role of MLF proteins in the cell has remained elusive. Here, we describe a proteomics approach that identifies MLF as a member of a nuclear chaperone complex containing a DnaJ protein, BCL2-associated anthanogene 2, and Hsc70. This complex associates with chromatin and regulates the expression of target genes. The MLF complex is bound to sites of nucleosome depletion and sites containing active chromatin marks (e.g., H3K4me3 and H3K4me1). Hence, MLF binding is enriched at promoters and enhancers. Additionally, the MLF-chaperone complex functions to regulate transcription factor stability, including the RUNX transcription factor involved in hematopoiesis. Although Hsc70 and other co-chaperones have been shown to play a role in nuclear translocation of a variety of proteins including transcription factors, our findings suggest that MLF and the associated co-chaperones play a direct role in modulating gene transcription.

KEYWORDS:

MLF; chaperone; enhancer; promoter; transcription

PMID:
27984043
PMCID:
PMC5841623
DOI:
10.1016/j.jmb.2016.10.026
[Indexed for MEDLINE]
Free PMC Article

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