{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T08:42:51Z","timestamp":1766133771726,"version":"3.38.0"},"reference-count":67,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The T cell-surface glycoprotein CD6 is a modulator of cellular responses and has been implicated in several autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis. During Ag presentation, CD6 is targeted to the immunological synapse in a ligand binding-dependent manner, in which CD6 domain 3 directly contacts CD166, expressed on the APC. T cell activation results in the induction of CD6\u0394d3, an alternatively spliced isoform that lacks the ligand-binding domain and thus no longer localizes at the immunological synapse. In this study, we investigated the molecular mechanisms regulating the expression of CD6\u0394d3 upon human primary T cell activation. Using chromatin immunoprecipitation, we observed an increase in RNA polymerase II occupancy along the CD6 gene and augmented CD6 transcription. We showed that activation leads to transcription-related chromatin modifications, revealed by higher CD6 acetylation levels. Modulation of chromatin conformation using a histone deacetylase inhibitor that increases transcription rate causes an increase of exon 5 skipping. We further showed that the splicing factor SRSF1 binds to a regulatory element in CD6 intron 4, activating exon 5 splicing and promoting exon 5 inclusion. Concomitant with T cell activation-induced exon 5 skipping, we observed a downregulation of SRSF1. Using RNA immunoprecipitation, we showed that in activated T cells, SRSF1 recruitment to the CD6 transcript is impaired by increased chromatin acetylation levels. We propose that upon T cell activation, SRSF1 becomes limiting, and its function in CD6 exon 5 splicing is countered by an increase in CD6 transcription, dependent on chromatin acetylation.<\/jats:p>","DOI":"10.4049\/jimmunol.1400038","type":"journal-article","created":{"date-parts":[[2014,6,3]],"date-time":"2014-06-03T00:27:19Z","timestamp":1401755239000},"page":"391-399","source":"Crossref","is-referenced-by-count":29,"title":["T Cell Activation Regulates CD6 Alternative Splicing by Transcription Dynamics and SRSF1"],"prefix":"10.1093","volume":"193","author":[{"given":"V\u00e2nia G","family":"da Gl\u00f3ria","sequence":"first","affiliation":[{"name":"Grupo Regula\u00e7\u00e3o Gen\u00e9tica, Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto 4150-180 ,","place":["Portugal"]}]},{"given":"Mafalda","family":"Martins de Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Grupo Activa\u00e7\u00e3o Celular e Express\u00e3o Gen\u00e9tica, Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto 4150-180 ,","place":["Portugal"]},{"name":"Instituto de Investiga\u00e7\u00e3o em Ci\u00eancias da Vida e da Saude, Escola de Ci\u00eancias da Saude, Universidade do Minho , Braga 4710-057 ,","place":["Portugal"]},{"name":"ICVS\/3B's Laborat\u00f3rio Associado , Braga\/Guimar\u00e3es 4806-909 ,","place":["Portugal"]}]},{"given":"Ana","family":"Mafalda Santos","sequence":"additional","affiliation":[{"name":"Grupo Activa\u00e7\u00e3o Celular e Express\u00e3o Gen\u00e9tica, Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto 4150-180 ,","place":["Portugal"]}]},{"given":"Rafaela","family":"Leal","sequence":"additional","affiliation":[{"name":"Grupo Regula\u00e7\u00e3o Gen\u00e9tica, Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto 4150-180 ,","place":["Portugal"]}]},{"given":"S\u00e9rgio F","family":"de Almeida","sequence":"additional","affiliation":[{"name":"Instituto de Medicina Molecular, Faculdade de Medicina, Universidade Lisboa , Lisboa 1649-028 ,","place":["Portugal"]}]},{"given":"Alexandre M","family":"Carmo","sequence":"additional","affiliation":[{"name":"Grupo Activa\u00e7\u00e3o Celular e Express\u00e3o Gen\u00e9tica, Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto 4150-180 ,","place":["Portugal"]},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto , Porto 4050-313 ,","place":["Portugal"]}]},{"given":"Alexandra","family":"Moreira","sequence":"additional","affiliation":[{"name":"Grupo Regula\u00e7\u00e3o Gen\u00e9tica, Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto 4150-180 ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2014,7,1]]},"reference":[{"key":"2025030707192488300_r1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.4049\/jimmunol.127.3.987","article-title":"A novel human T cell antigen preferentially expressed on mature T cells and shared by both well and poorly differentiated B cell leukemias and lymphomas","volume":"127","author":"Kamoun","year":"1981","journal-title":"J. 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