TAILIEUCHUNG - Báo cáo khoa học: The Runx3 distal transcript encodes an additional transcriptional activation domain

The runt family transcriptional regulator, Runx3, is upregulated during the differentiation of CD8 single-positive thymocytes and is expressed in peri-pheral CD8 + T cells. Mice carrying targeted deletions in Runx3 have severe defects in the development and activation of CD8 + T cells, resulting in decreased CD8 + T-cell numbers, aberrant coexpression of CD4, and failure to expand CD8 + effector cells after activation in vivo orin vitro. | ỊFEBS Journal The Runx3 distal transcript encodes an additional transcriptional activation domain David D. Chung1 Kazuho Honda2 Lorraine Cafuir2 Marcia McDuffie2 3 and David Wotton1 1 Center for CellSignaling and Department of Biochemistry and Molecular Genetics University of Virginia Schoolof Medicine Charlottesville VA USA 2 Department of Microbiology University of Virginia Schoolof Medicine Charlottesville VA USA 3 Department of Medicine University of Virginia Schoolof Medicine Charlottesville VA USA Keywords cell differentiation runt domain Runx3 transcription Correspondence M. McDuffie University of Virginia School of Medicine Aurbach MedicalResearch Building Box 801390 FedEx room 1253 Charlottesville VA 22908 USA Fax 1 434 243 9143 Tel 1 434 924 1707 E-mail mjm7e@ D. Wotton Center for Cell Signaling University of Virginia Room 7008 HospitalWest Hsc 800577 Charlottesville VA 22908 USA Fax 1 434 924 1236 Tel 1 434 243 6752 E-mail dw2p@ Present address Department of Pathology Tokyo Women s MedicalUniversity Tokyo Japan Received 5 February 2007 revised 5 April 2007 accepted 9 May 2007 doi The runt family transcriptional regulator Runx3 is upregulated during the differentiation of CD8 single-positive thymocytes and is expressed in peripheral CD8 T cells. Mice carrying targeted deletions in Runx3 have severe defects in the development and activation of CD8 T cells resulting in decreased CD8 T-cell numbers aberrant coexpression of CD4 and failure to expand CD8 effector cells after activation in vivo or in vitro. Expression of each of the three vertebrate runt family members including Runx3 is controlled by two promoters that generate proteins with alternative N-terminal sequences. The longer N-terminal region of Runx3 expressed from the distal promoter is highly conserved among family members and across species. We show that transcripts from the distal Runx3 promoter are selectively expressed in mature CD8 T .

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