Sayyed K Zaidi

Publications (3)5.53 Total impact

• Article: HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition.

  Angela Miele, Corey D Braastad, William F Holmes, Partha Mitra, Ricardo Medina, Ronglin Xie, Sayyed K Zaidi, Xin Ye, Yue Wei, J Wade Harper, Andre J van Wijnen, Janet L Stein, Gary S Stein
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  ABSTRACT: Genome replication in eukaryotic cells necessitates the stringent coupling of histone biosynthesis with the onset of DNA replication at the G1/S phase transition. A fundamental question is the mechanism that links the restriction (R) point late in G1 with histone gene expression at the onset of S phase. Here we demonstrate that HiNF-P, a transcriptional regulator of replication-dependent histone H4 genes, interacts directly with p220(NPAT), a substrate of cyclin E/CDK2, to coactivate histone genes during S phase. HiNF-P and p220 are targeted to, and colocalize at, subnuclear foci (Cajal bodies) in a cell cycle-dependent manner. Genetic or biochemical disruption of the HiNF-P/p220 interaction compromises histone H4 gene activation at the G1/S phase transition and impedes cell cycle progression. Our results show that HiNF-P and p220 form a critical regulatory module that directly links histone H4 gene expression at the G1/S phase transition to the cyclin E/CDK2 signaling pathway at the R point.
  Molecular and Cellular Biology 08/2005; 25(14):6140-53. · 5.53 Impact Factor
• Article: HiNF-P directly links the cyclin E/CDK2/p220NPAT pathway to histone H4 gene regulation at the G1/S phase cell cycle transition

  Angela Miele, Corey D Braastad, William F Holmes, Partha Mitra, Ricardo F. Medina, Ronglin Xie, Sayyed K Zaidi, Xin Ye, Yue Wei, J Wade Harper, Andre J van Wijnen, Janet L Stein, Gary S Stein
  [show abstract] [hide abstract]
  ABSTRACT: Genome replication in eukaryotic cells necessitates the stringent coupling of histone biosynthesis with the onset of DNA replication at the G1/S phase transition. A fundamental question is the mechanism that links the restriction (R) point late in G1 with histone gene expression at the onset of S phase. Here we demonstrate that HiNF-P, a transcriptional regulator of replication-dependent histone H4 genes, interacts directly with p220(NPAT), a substrate of cyclin E/CDK2, to coactivate histone genes during S phase. HiNF-P and p220 are targeted to, and colocalize at, subnuclear foci (Cajal bodies) in a cell cycle-dependent manner. Genetic or biochemical disruption of the HiNF-P/p220 interaction compromises histone H4 gene activation at the G1/S phase transition and impedes cell cycle progression. Our results show that HiNF-P and p220 form a critical regulatory module that directly links histone H4 gene expression at the G1/S phase transition to the cyclin E/CDK2 signaling pathway at the R point.
  Sayyed K. Zaidi.
• Article: Identification of HiNF-P, a key activator of cell cycle-controlled histone H4 genes at the onset of S phase

  Partha Mitra, Ronglin Xie, Ricardo F. Medina, Hayk Hovhannisyan, Sayyed K Zaidi, Yue Wei, J Wade Harper, Janet L Stein, Andre J van Wijnen, Gary S Stein
  [show abstract] [hide abstract]
  ABSTRACT: At the G(1)/S phase cell cycle transition, multiple histone genes are expressed to ensure that newly synthesized DNA is immediately packaged as chromatin. Here we have purified and functionally characterized the critical transcription factor HiNF-P, which is required for E2F-independent activation of the histone H4 multigene family. Using chromatin immunoprecipitation analysis and ligation-mediated PCR-assisted genomic sequencing, we show that HiNF-P interacts with conserved H4 cell cycle regulatory sequences in vivo. Antisense inhibition of HiNF-P reduces endogenous histone H4 gene expression. Furthermore, we find that HiNF-P utilizes NPAT/p220, a substrate of the cyclin E/cyclin-dependent kinase 2 (CDK2) kinase complex, as a key coactivator to enhance histone H4 gene transcription. The biological role of HiNF-P is reflected by impeded cell cycle progression into S phase upon antisense-mediated reduction of HiNF-P levels. Our results establish that HiNF-P is the ultimate link in a linear signaling pathway that is initiated with the growth factor-dependent induction of cyclin E/CDK2 kinase activity at the restriction point and culminates in the activation of histone H4 genes through HiNF-P at the G(1)/S phase transition.
  Sayyed K. Zaidi.