Thymosin β4 (Tβ4) is an actin monomer sequestering protein that may have a critical role in modulating the dynamics of actin polymerization and depolymerization in nonmuscle cells. Its regulatory role is consistent with the many examples of transcriptional regulation of Tβ4 and of tissue-specific expression. Furthermore, lymphocytes have a unique Tβ4 transcript relative to the ubiquitous transcript found in many other tissues and cells. To determine how Tβ4 gene expression is regulated and how the alternative transcripts are derived, we cloned the mouse Tβ4 gene. We established that there is a single mouse Tβ4 gene and found that the lymphoid-specific transcript is generated by extending the ubiquitous exon 1 with an alternate downstream splice site. The transcription start site is defined by primer extension analysis, and the 5′-flanking region has many of the characteristics of a promoter. It is pyrimidine-rich and contains typical promoter elements, including a GC box, an initiator site, and consensus transcription factor binding sites. The mouse Tβ4 gene locus (Ptmb4) is located by interspecific backcross mapping to the distal region of the mouse X chromosome, linked to Btk and Gja6.
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