Transcription factor abundance controlled by an auto-regulatory mechanism involving a transcription start site switch.
A transcriptional feedback loop is the simplest and most direct means for a transcription factor to provide an increased stability of gene expression. In this work performed in human cells, we reveal a new negative auto-regulatory mechanism involving an alternative transcription start site (TSS) usage. Using the activating transcription factor ZNF143 as a model, we show that the ZNF143 low-affinity binding sites, located downstream of its canonical TSS, play the role of protein sensors to induce the up- or down-regulation of ZNF143 gene expression. We uncovered that the TSS switch that mediates this regulation implies the differential expression of two transcripts with an opposite protein production ability due to their different 5' untranslated regions. Moreover, our analysis of the ENCODE data suggests that this mechanism could be used by other transcription factors to rapidly respond to their own aberrant expression level.
Architecture et Réactivité de l'ARN, Université de Strasbourg, CNRS, IBMC, 15 Rue René Descartes, 67084 Strasbourg, France.
Richard Patryk
RP
Ngondo
Philippe
P
Carbon
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site
D015534:Trans-Activators; C114253:ZNF143 protein, human