Transcription factor Sp1 regulates mitotic chromosome assembly and segregation

Abstract

Aneuploidy is a pervasive feature of cancer cells that results from chromosome missegregation. Several transcription factors have been associated with aneuploidy; however, no studies to date have demonstrated that mammalian transcription factors directly regulate chromosome segregation during mitosis. Here, we demonstrate that the ubiquitously expressed transcription factor specificity protein 1 (Sp1), which we have previously linked to aneuploidy, has a mitosis-specific role regulating chromosome segregation. We find that Sp1 localizes to mitotic centromeres and auxin-induced rapid Sp1 degradation at mitotic onset results in chromosome segregation errors and aberrant mitotic progression. Furthermore, rapid Sp1 degradation results in anomalous mitotic chromosome assembly characterized by loss of condensin complex I localization to mitotic chromosomes and chromosome condensation defects. Consistent with these defects, Sp1 degradation results in reduced chromosome passenger complex activity and histone H3 serine 10 phosphorylation during mitosis, which is essential for condensin complex I recruitment and chromosome condensation. Together, these data provide the first evidence of a mammalian transcription factor acting specifically during mitosis to regulate chromosome segregation.

Integration of ATAC-Seq and RNA-Seq Analysis to Identify Key Genes in the Longissimus Dorsi Muscle Development of the Tianzhu White Yak

“…Sp1, a ubiquitously expressed mammalian transcription factor, plays a pivotal role in maintaining genome integrity through diverse mechanisms [ 58 , 59 ]. Recent research has revealed that Sp1 is essential for the assembly of mitotic chromosomes, thereby facilitating cell proliferation [ 60 ]. In vivo studies on YY1 knockout mice derived from skeletal muscle satellite cells have demonstrated that inducible deletion of YY1 significantly impedes the process of muscle repair caused by acute damage and exacerbates the dystrophic phenotype resulting from chronic injury [ 61 ].…”