{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T19:48:03Z","timestamp":1782157683896,"version":"3.54.5"},"reference-count":45,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"name":"National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["F31DK131639"],"award-info":[{"award-number":["F31DK131639"]}]},{"name":"National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01DK082590"],"award-info":[{"award-number":["R01DK082590"]}]},{"name":"National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01DK102950"],"award-info":[{"award-number":["R01DK102950"]}]},{"name":"National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01DK106412"],"award-info":[{"award-number":["R01DK106412"]}]},{"name":"National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["R01DK140904"],"award-info":[{"award-number":["R01DK140904"]}]},{"name":"National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases","award":["T32GM136444"],"award-info":[{"award-number":["T32GM136444"]}]},{"name":"University of Colorado Diabetes Research Center","award":["P30DK116073"],"award-info":[{"award-number":["P30DK116073"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>NKX2.2 is a transcription factor that regulates pancreatic islet \u03b2-cell identity and function; however, cofactor proteins that modulate the functional activity of NKX2.2 in \u03b2-cells are relatively unexplored. An unbiased proteomics screen identified chromodomain helicase DNA-binding protein 4 (CHD4) as an NKX2.2 interacting partner. CHD4 is a nucleosome remodeler that directs the appropriate differentiation, maturation and function of many cell types. To characterize the roles of CHD4 in \u03b2-cells, we generated Chd4 \u03b2-knockout (\u03b2KO) mice. Deletion of Chd4 substantially impaired the function of \u03b2-cells. The Chd4 \u03b2KO mice became diabetic due to the disruption of islet integrity, calcium signaling, and downregulation of essential \u03b2-cell regulatory genes. We also discovered CHD4 is required to bind at and repress non\u2013\u03b2-cell genes, including Kcnj5, the gene that encodes the G protein-activated inward rectifier potassium channel 4 (GIRK4) in \u03b2-cells. Aberrant upregulation of GIRK4 causes impaired glucose-stimulated insulin secretion. These studies demonstrate that CHD4 is an essential transcriptional cofactor of NKX2.2 that is required for the proper maturation and function of pancreatic \u03b2-cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>NKX2.2 interacts with the nucleosome remodeling and deacetylase complex through its interaction with chromodomain helicase DNA-binding protein 4 (CHD4). Deletion of CHD4 from developing pancreatic \u03b2-cells in mice causes diabetes due to a loss of islet integrity, disrupted calcium signaling, and impaired insulin secretion. \u03b2-Cells lacking CHD4 inappropriately upregulate the G protein-activated inward rectifier potassium channel 4 (GIRK4) potassium channel; inhibition of GIRK4 rescues the insulin secretion defect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0945","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:42:41Z","timestamp":1777902161000},"page":"1189-1200","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":0,"title":["CHD4 and NKX2.2 Cooperate to Regulate \u03b2-Cell Function by Repressing Non\u2013\u03b2-Cell Gene Programs"],"prefix":"10.2337","volume":"75","author":[{"given":"Dylan","family":"Sarbaugh","sequence":"first","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thais Gaia","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Guney","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McKenna R.","family":"Casey","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria M.","family":"Hoelscher","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cole R.","family":"Michel","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Facility, School of Pharmacy, University of Colorado Anschutz Medical Campus 2 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen L.","family":"Wells","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard K.P.","family":"Benninger","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus 1 , Aurora, 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