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

Authors

Jamie O. Dyer, Rockhurst University
Arnob Dutta, University of Rhode Island
Madelaine Gogol, Stowers Institute for Medical Research
Vikki M. Weake, Purdue University
George Dialynas, Stowers Institute for Medical Research
Xilan Wu, Stowers Institute for Medical Research
Christopher Seidel, Stowers Institute for Medical Research
Ying Zhang, Stowers Institute for Medical ResearchFollow
Laurence Florens, Stowers Institute for Medical Research
Michael P. Washburn, Stowers Institute for Medical Research
Susan M. Abmayr, Stowers Institute for Medical Research
Jerry L. Workman, Stowers Institute for Medical Research

Document Type

Article

Date of Original Version

6-30-2017

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.

Publication Title, e.g., Journal

Journal of Molecular Biology

Volume

429

Issue

13

Citation/Publisher Attribution

Dyer, Jamie O., Arnob Dutta, Madelaine Gogol, Vikki M. Weake, George Dialynas, Xilan Wu, Christopher Seidel, Ying Zhang, Laurence Florens, Michael P. Washburn, Susan M. Abmayr, and Jerry L. Workman. "Myeloid Leukemia Factor Acts in a Chaperone Complex to Regulate Transcription Factor Stability and Gene Expression." Journal of Molecular Biology 429, 13 (2017): 2093-2107. doi: 10.1016/j.jmb.2016.10.026.