title: Multiple modes of chromatin remodeling by Forkhead box proteins.
abstract: Forkhead box (FOX) proteins represent a large family of transcriptional regulators unified by their DNA binding domain (DBD) known as a 'forkhead' or 'winged helix' domain. Over 40 FOX genes have been identified in the mammalian genome. FOX proteins share significant sequence similarities in the DBD which allow them to bind to a consensus DNA response element. However, their modes of action are quite diverse as they regulate gene expression by acting as pioneer factors, transcription factors, or both. This review focuses on the mechanisms of chromatin remodeling with an emphasis on three sub-classes-FOXA, FOXO, and FOXP members. FOXA proteins serve as pioneer factors to open up local chromatin structure and thereby increase accessibility of chromatin to factors regulating transcription. FOXP proteins, in contrast, function as classic transcription factors to recruit a variety of chromatin modifying enzymes to regulate gene expression. FOXO proteins represent a hybrid subclass having dual roles as pioneering factors and transcription factors. A subset of FOX proteins interacts with condensed mitotic chromatin and may function as 'bookmarking' agents to maintain transcriptional competence at specific genomic sites. The overall diversity in chromatin remodeling function by FOX proteins is related to unique structural motifs present within the DBD flanking regions that govern selective interactions with core histones and/or chromatin coregulatory proteins. This article is part of a Special Issue entitled: Chromatin in time and space.
authors.affiliation: Division of Therapeutic Proteins, Office of Biotechnology Products, Office of Pharmaceutical Sciences, Center for Drug Evaluation and Research, Food and Drug administration, Bethesda, MD 20892, USA.
authors.forename: Avin S
authors.initials: AS
authors.lastname: Lalmansingh
authors.forename: Sudipan
authors.initials: S
authors.lastname: Karmakar
authors.forename: Yetao
authors.initials: Y
authors.lastname: Jin
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Nagaich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly; D017124:Conserved Sequence; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D051858:Forkhead Transcription Factors; D006657:Histones