Year: 2022
Type: article
Abstract: Forkhead box H1 (FoxH1) is an essential maternal pioneer factor during embryonic development that binds to specific GG/GT-containing DNA target sequences. Here we have determined high-resolution structures of three FoxH1 proteins (from human, frog and fish species) and four DNAs to clarify the way in which FoxH1 binds to these sites. We found that the protein-DNA interactions extend to both the minor and major DNA grooves and are thus almost twice as extensive as those of other FOX family members. Moreover, we identified two specific amino acid changes in FoxH1 that allowed the recognition of GG/GT motifs. Consistent with the pioneer factor activity of FoxH1, we found that its affinity for nucleosomal DNA is even higher than for linear DNA fragments. The structures reported herein illustrate how FoxH1 binding to distinct DNA sites provides specificity and avoids cross-regulation by other FOX proteins that also operate during the maternal-zygotic transition and select canonical forkhead sites.
Source: Nature Communications
Authors: Radoslaw Pluta, Eric Aragón, Nicholas A. Prescott, Lidia Ruiz, Rebeca A. Mees, Blazej Baginski, Julia R. Flood, Pau Martin-Malpartida, Joan Massagué, Yael David, Maria J. Macias
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Funders: National Science Foundation, U.S. Department of Health and Human Services, Commonwealth Foundation, Memorial Sloan-Kettering Cancer Center, Fundación BBVA, Institute for Research in Biomedicine, Robertson Foundation, Pershing Square Sohn Cancer Research Alliance, Parker Institute for Cancer Immunotherapy, Centres de Recerca de Catalunya, European Commission, Generalitat de Catalunya, Ministerio de Economía y Competitividad, Institució Catalana de Recerca i Estudis Avançats, Banco Bilbao Vizcaya Argentaria, Universitat de Barcelona, National Institutes of Health, Agència de Gestió d'Ajuts Universitaris i de Recerca, European Regional Development Fund, Agencia Estatal de Investigación, National Cancer Institute, National Institute of General Medical Sciences
Awards: G1007166040, G1175115578, G1558408032, G1676388581, G1818556086, G2042483231, G2051006376, G2064873908, G210041235, Tri-Institutional PhD Program in Chemical Biology, G2262748287, G2601397997, G288263039, G289723095, G3005324705, G300979063, G34346518, G3480869486, G3681454997, G3723734402, G4042783231, G4043403084, G410571670, G425668148, G434337789, G438478669, Biochemical studies of aberrant chromatin regulation in cancer, G451917667, G4583515593, G4766705570, G5080475149, G5852091828, G5967599077, G6656126374, MSK SPORE in Lymphoma, G69051668, G707234588, COFUND BIST PREDOCTORAL PROGRAMME, G7434936867, G7466406081, G7556015768, G7796364618, Investigating histone glycation as a new dynamic epigenetic mark, G9000003249, G9000035526, G9000134467, Cancer Center Support Grant, The TGFÃÂÃÂÃÂò Signaling Pathway in Development and Cancer, G929308097
OpenAlex ID: W4310011034