title: GATA3 cooperates with PARP1 to regulate CCND1 transcription through modulating histone H1 incorporation.
abstract: The transcription factor GATA3 is a key regulator of mammary gland development and a definitive marker of luminal breast cancer. However, the molecular mechanisms underlying the role of GATA3 in breast carcinogenesis is still not fully understood. We report here that GATA3 promotes cell proliferation and tumorigenesis by facilitating the G1/S transition through its transcription regulation of the CCND1 gene in breast cancer cells. We found that GATA3 is physically associated with poly-ADP ribose polymerase-1 (PARP1), an enzyme modifying nuclear proteins by poly(ADP-ribosyl)ation. We showed that PARP1 acts as a transcription coactivator for GATA3 in breast cancer cells and demonstrated that GATA3 cooperates with PARP1 in transactivation of the CCND1 gene. We demonstrated that PARP1 competes with linker histone H1 to maintain a transcriptional competent chromatin environment for CCND1 gene. Our results unveiled a molecular basis for the coordinated regulation between GATA3 and PARP1 in transcription activation, providing a mechanism for GATA3 in breast carcinogenesis.
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: L
authors.initials: L
authors.lastname: Shan
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Ding
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: C
authors.initials: C
authors.lastname: Xuan
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shang
authors.affiliation: Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, China.
authors.forename: L
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: C530104:CCND1 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D006657:Histones; D010446:Peptide Fragments; D012333:RNA, Messenger; D019938:Cyclin D1; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases