title: Myeloid Leukemia Factor Acts in a Chaperone Complex to Regulate Transcription Factor Stability and Gene Expression.
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.
authors.affiliation: Department of Biology, Rockhurst University, Kansas City, MO 64110, USA.
authors.forename: Jamie O
authors.initials: JO
authors.lastname: Dyer
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA.
authors.forename: Arnob
authors.initials: A
authors.lastname: Dutta
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Gogol
authors.affiliation: Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Vikki M
authors.initials: VM
authors.lastname: Weake
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: George
authors.initials: G
authors.lastname: Dialynas
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Xilan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Seidel
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: 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.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: 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.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA. Electronic address: jlw@stowers.org.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
mesh_terms: D018797:Cell Cycle Proteins; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000378:metabolism; D015870:Gene Expression; D018832:Molecular Chaperones; D011485:Protein Binding; D055503:Protein Multimerization; D011506:Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C100852:MLF1 protein, human; C468117:Mlf protein, Drosophila; D018832:Molecular Chaperones; D011506:Proteins; D014157:Transcription Factors
keywords: MLF; chaperone; enhancer; promoter; transcription