The nuclear matrix protein NMP-1 is the transcription factor YY1.

Abstract

NMP-1 was initially identified as a nuclear matrix-associated DNA-binding factor that exhibits sequencespecific recognition for the site IV regulatory element of a histone H4 gene. This distal promoter domain is a nuclear matrix interaction site. In the present study, we show that NMP-1 is the multifunctional transcription factor YY1. Gelshift and Western blot analyses demonstrate that NMP-1 is immunoreactive with YY1 antibody. Furthermore, purified YY1 protein specifically recognizes site IV and reconstitutes the NMP-1 complex. Western blot and gel-shift analyses indicate that YY1 is present within the nuclear matrix. In situ immunofluorescence studies show that a significant fraction of YY1 is localized in the nuclear matrix, principally but not exclusively associated with residual nucleoli. Our results confirm that NMP-1/YY1 is a ubiquitous protein that is present in both human cells and in rat osteosarcoma ROS 17/2.8 cells. The finding that NMP-1 is identical to YY1 suggests that this transcriptional regulator may mediate gene-matrix interactions. Our results are consistent with the concept that the nuclear matrix may functionally compartmentalize the eukaryotic nucleus to support regulation ofgene expression.The nuclear matrix has been linked to multiple functions that mediate the control of gene expression within the nucleus (1-8). This component of the nuclear architecture provides the internal scaffold of the nucleus; it consists of a peripheral lamina-pore complex, an internal filamentous ribonucleoprotein network, and residual nucleoli (2, 8). The nuclear matrix plays an important role in higher-order organization of chromatin and the tethering of actively transcribed genes via matrix-associated regions (MARs) or scaffold-attached regions (SARs) (9-18). Involvement of the nuclear matrix in RNA processing has been demonstrated; heterogeneous nuclear RNAs, small nuclear RNAs, and RNA processing intermediates are enriched in the nuclear matrix; ribonucleoprotein particles are components of nuclear matrix structure (19)(20)(21)(22) (35) have shown that c-myc inhibits both the repressor and activator functions of YY1. In the c-fos promoter YY1 appears to act by bending DNA to regulate contact between other factors (37). Thus, YY1 has been implicated in several possible functional roles related to transcription.In this study, we unequivocally establish that the nuclear matrix protein NMP-1 is the transcriptional regulator YY1 and demonstrate that NMP-1/YY1 is localized to the nuclear matrix in situ as well as by biochemical analyses. MATERIALS AND METHODSNuclear Protein Preparations. Nuclear extracts were prepared as described (38) The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Action of Transcription Factors in the Control of Transferrin Receptor Expression in Human Brain Endothelium

“…Since the shorter isoform, seen in brain endothelium was detected by antibody to the whole YY-1 (Figure 9(a)), but not by antibody to the C-terminus ( Figure 9(b)), this implies that the short isoform lacks a C-terminal segment. YY1 proteins of these sizes have been shown previously by in vitro translation and Western blots, 22 to be YY1 and a truncated form of YY1 at the C-terminus, respectively. 23 This suggests that in hCMEC/D3 cells YY1 is present, but truncation of the YY1 protein prevents its interaction with DNA -note that the C-terminus of YY1 contains its four DNA-binding zinc-fingers.…”

Mitotic partitioning and selective reorganization of tissue-specific transcription factors in progeny cells

“…I n the interphase nucleus, many tissue-restricted transcription factors are architecturally organized at punctate subnuclear sites that are associated with the nuclear matrix scaffold (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). These nuclear matrix-associated intranuclear foci are linked to transcriptional activation and suppression and contain coregulatory proteins and signaling molecules (19-22, ‡).…”

Enhanceosome Formation over the Beta Interferon Promoter Underlies a Remote-Control Mechanism Mediated by YY1 and YY2

“…YY1 was originally described as nuclear matrix protein 1 (NMP-1) by Guo et al (12), i.e., a nuclear matrix-associated DNA-binding factor with sequence-specific recognition of a regulatory element next to a histone H4 gene. The finding that NMP-1 is YY1 suggests that this transcriptional regulator may mediate gene-matrix interactions.…”