The FOG family of transcriptional co-factors is composed of two members in mammals: FOG-1 and FOG-2. Both have been shown to bind to GATA factors and function as transcriptional co-repressors in specific cell and promoter contexts. We have previously defined a novel repression domain localized to the N-terminus of each FOG family member, the FOG repression motif, which is necessary for FOG-mediated transcriptional repression. In this report, we describe the identification and characterization of a novel isoform of FOG-2 lacking the FOG repression motif. In contrast to full-length FOG-2, this isoform is expressed predominately in the embryonic and adult heart. It can bind GATA4 avidly, but is unable to repress GATA4-mediated activation of cardiac-restricted gene promoters. Together, these results suggest that FOG-2 repressive activity may be modulated by the generation of isoforms of FOG-2 lacking the FOG repression motif.
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http://dx.doi.org/10.1016/j.bbrc.2007.04.008 | DOI Listing |
Nat Commun
November 2022
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic heterogeneity, here we perform integrated genomic analyses of mixed histology bladder cancers with separable regions of urothelial and squamous differentiation. We find that squamous differentiation is a marker of intratumoral genomic and immunologic heterogeneity in patients with bladder cancer and a biomarker of intrinsic immunotherapy resistance.
View Article and Find Full Text PDFSex Dev
February 2022
Department of Molecular Biology, Rowan University SOM, Stratford, New Jersey, USA.
Background: Animal germ cells differentiate as sperm or as oocytes. These sexual fates are controlled by complex regulatory pathways to ensure that the proper gametes are made at the appropriate times.
Summary: Nematodes like Caenorhabditis elegans and its close relatives are ideal models for studying how this regulation works, because the XX animals are self-fertile hermaphrodites that produce both sperm and oocytes.
Front Oncol
July 2021
Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Leukemic stem cell (LSC) is thought to be responsible for chronic myelogenous leukemia (CML) initiation and relapse. However, the inherent regulation of LSCs remains largely obscure. Herein, we integratedly analyzed miRNA and gene expression alterations in bone marrow (BM) LinSca1c-Kit cells (LSKs) of a tet-off inducible CML mouse model, Scl/tTA-BCR/ABL (BA).
View Article and Find Full Text PDFGenetics
March 2021
Department of Biological Sciences, Marquette University, 1428 W. Clybourn Ave, PO Box 1881, Milwaukee, WI 53233, USA.
Posttranscriptional regulation of gene expression, typically effected by RNA-binding proteins, microRNAs (miRNAs), and translation initiation factors, is essential for normal germ cell function. Numerous miRNAs have been detected in the germline; however, the functions of specific miRNAs remain largely unknown. Functions of miRNAs have been difficult to determine as miRNAs often modestly repress target mRNAs and are suggested to sculpt or fine tune gene expression to allow for the robust expression of cell fates.
View Article and Find Full Text PDFCell Rep
June 2018
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:
FOG-3 is a master regulator of sperm fate in Caenorhabditis elegans and homologous to Tob/BTG proteins, which in mammals are monomeric adaptors that recruit enzymes to RNA binding proteins. Here, we determine the FOG-3 crystal structure and in vitro demonstrate that FOG-3 forms dimers that can multimerize. The FOG-3 multimeric structure has a basic surface potential, suggestive of binding nucleic acid.
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