The Yin Yang-1 (YY1) protein undergoes a DNA-replication-associated switch in localization from the cytoplasm to the nucleus at the onset of S phase

Abstract

The essential Yin Yang-1 gene (YY1) encodes a ubiquitous, conserved, multifunctional zinc-finger transcription factor in animals. The YY1 protein regulates initiation, activation, or repression of transcription from a variety of genes required for cell growth, development, differentiation, or tumor suppression, as well as from genes in some retroviruses and DNA viruses. Among the specific functions attributed to YY1 is a role in cell-cycle-specific upregulation of the replication-dependent histone genes. The YY1 protein binds to the histone alpha element, a regulatory sequence found in all replication-dependent histone genes. We therefore examined the abundance, DNA-binding activity and localization of the YY1 protein throughout the cell cycle in unperturbed, shake-off-synchronized Chinese hamster ovary and HeLa cells. We found that, whereas the DNA-binding activity of YY1 increased dramatically early in S phase, the YY1 mRNA and protein levels did not. YY1 changed subcellular distribution patterns during the cell cycle, from mainly cytoplasmic at G1 to mainly nuclear at early and middle S phase, then back to primarily cytoplasmic later in S phase. Nuclear accumulation of YY1 near the G1/S boundary coincided with both an increase in YY1 DNA-binding activity and the coordinate up-regulation of the replication-dependent histone genes. The DNA synthesis inhibitor aphidicolin caused a nearly complete loss of nuclear YY1, whereas addition of caffeine or 2-aminopurine to aphidicolin-treated cells restored both DNA synthesis and YY1 localization in the nucleus. These findings reveal a mechanism by which YY1 localization is coupled to DNA synthesis and responsive to cell-cycle signaling pathways. Taken together, our results provide insight into how YY1 might participate in the cell-cycle control over a variety of nuclear events required for cell division and proliferation.

The Developmental Regulator Protein Gon4l Associates with Protein YY1, Co-repressor Sin3a, and Histone Deacetylase 1 and Mediates Transcriptional Repression

“…2C). FLAG-Gon4l was detected in the nucleus, whereas YY1 was seen in both the cytoplasm and the nucleus as previously reported (35). Among 60 cells staining positive for both proteins, 57 (ϳ95%) showed overlapping nuclear localization of YY1 and Gon4l.…”

Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression

“…Cell treatment with RA did not affect YY1 localization in cytoplasmic and nuclear regions, although it did induce Dicer1 in the nuclear compartment (supplemental Figure 5B). RA treatment also increased YY1-Dicer1, YY1-Mimic-223, and Dicer1-Mimic-223 colocalization in the nuclear periphery, a site of preferential YY1 and heterochromatin localization 44 ( Figure 6B; supplemental Figure 5A-C). These changes were not observed when Mimic-NC was used (supplemental Figure 5A-C), thus supporting the formation of a repressive complex composed by YY1, Dicer1, and miR-223.…”

The involvement of the transcription factor Yin Yang 1 in cancer development and progression

“…As a result, YY1 develops intracellular networks that allow it to induce multiple functions in transcriptional initiation, activation and repression, ultimately leading to the regulation of normal cell growth and survival. 13 Yin Yang 1 and Tumorigenesis p53. The putative role of YY1 in tumorigenesis is supported by its known interaction with the cell cycle regulation.…”