{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:01:01Z","timestamp":1789696861536,"version":"4.0.1"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"32","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,8,7]]},"abstract":"<jats:p>\n                    Here, we provide gain-of-function, loss-of function, and molecular evidence supporting genetic interactions between metastasis associated protein 1 (MTA1) and Six3 and between Six3 and\n                    <jats:italic>rhodopsin<\/jats:italic>\n                    . We discovered that MTA1 physically interacts with the\n                    <jats:italic>Six3<\/jats:italic>\n                    chromatin in a histone deacetylase-dependent manner, leading to transcriptional suppression of the\n                    <jats:italic>Six3<\/jats:italic>\n                    gene. MTA1 is also a Six3-interacting corepressor that contributes to a self-negative regulation of\n                    <jats:italic>Six3<\/jats:italic>\n                    transcription by Six3. In contrast, deletion of the\n                    <jats:italic>MTA1<\/jats:italic>\n                    alleles in murine embryonic fibroblasts or its knockdown in rat retinal ganglion cells stimulates Six3 expression. MTA1 inactivation in the\n                    <jats:italic>MTA1<\/jats:italic>\n                    -null mice results in an elevated Six3 level and proliferation of the retina cells with no obvious abnormities in eye formation. However, unexpectedly, we discovered an enhanced recruitment of Six3 to the\n                    <jats:italic>rhodopsin<\/jats:italic>\n                    chromatin in retina from the\n                    <jats:italic>MTA1<\/jats:italic>\n                    -null mice; Six3's homeodomain interacts with specific DNA elements in the\n                    <jats:italic>rhodopsin<\/jats:italic>\n                    promoter to stimulate its transcription, resulting in increased rhodopsin expression. Further, in holoprosencephaly patients, Six3 protein with a naturally occurring deletion mutation in the helix 3 of the homeodomain does not bind to\n                    <jats:italic>rhodopsin<\/jats:italic>\n                    DNA or stimulate\n                    <jats:italic>rhodopsin<\/jats:italic>\n                    transcription, implying a potential defective\n                    <jats:italic>rhodopsin<\/jats:italic>\n                    pathway in the affected holoprosencephaly patients. Further Six3 cooperates with Crx or NRL in stimulating transcription from the rhodopsin-luc. These findings reveal a previously unrecognized role for the MTA1 as an upstream modifier of Six3 and indicate that Six3 is a direct stimulator of rhodopsin expression, thus revealing a putative role for the MTA1\/Six3\/rhodopsin pathway in vertebrate eye.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0705878104","type":"journal-article","created":{"date-parts":[[2007,7,31]],"date-time":"2007-07-31T23:58:47Z","timestamp":1185926327000},"page":"13128-13133","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":61,"title":["Repression of Six3 by a corepressor regulates rhodopsin expression"],"prefix":"10.1073","volume":"104","author":[{"given":"Bramanandam","family":"Manavathi","sequence":"first","affiliation":[{"name":"Departments of *Molecular and Cellular Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaohua","family":"Peng","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cellular Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh K.","family":"Rayala","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cellular Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad H.","family":"Talukder","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cellular Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhua H.","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Optometry, University of Houston, Houston, TX 77004; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-An","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cellular Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seetharaman","family":"Balasenthil","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cellular Oncology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Cell Biology and Genetics, North Texas Health Science Center, Fort Worth, TX 76107;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"Frishman","sequence":"additional","affiliation":[{"name":"College of Optometry, University of Houston, Houston, TX 77004; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Departments of *Molecular and Cellular Oncology and"},{"name":"Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030;"},{"name":"Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2007,8,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/35050532"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00889"},{"key":"e_1_3_4_3_2","first-page":"105","volume":"19","author":"Toh Y","year":"2000","unstructured":"Y Toh, S Kuninaka, K Endo, T Oshiro, Y Ikeda, H Nakashima, H Baba, S Kohnoe, T Okamura, GL Nicolson, et al. 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