Article

Plzf Mediates Transcriptional Repression of HoxD Gene Expression through Chromatin Remodeling

Molecular Biology Program, Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Developmental Cell (Impact Factor: 9.71). 11/2002; 3(4):499-510. DOI: 10.1016/S1534-5807(02)00289-7
Source: PubMed

ABSTRACT

The molecular mechanisms that regulate coordinated and colinear activation of Hox gene expression in space and time remain poorly understood. Here we demonstrate that Plzf regulates the spatial expression of the AbdB HoxD gene complex by binding to regulatory elements required for restricted Hox gene expression and can recruit histone deacetylases to these sites. We show by scanning forced microscopy that Plzf, via homodimerization, can form DNA loops and bridge distant Plzf binding sites located within HoxD gene regulatory elements. Furthermore, we demonstrate that Plzf physically interacts with Polycomb proteins on DNA. We propose a model by which the balance between activating morphogenic signals and transcriptional repressors such as Plzf establishes proper Hox gene expression boundaries in the limb bud.

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    • "RA promotes differentiation of SSCs to differentiated spermatogonia through several mechanisms. One such mechanism is the down-regulation of promyelocytic leukemia zinc finger (PLZF) [48], which is specifically expressed in SSCs and upon deletion in mice impairs spermatogonial differentiation by affecting the expression of genes involved in SSC self-renewal and differentiation [49] [50] [51] [52]. One function of PLZF is to repress the expression of c-kit in spermatogonia [53] and as RA downregulates PLZF in SSC this could be one mechanism that controls the up-regulation of c-kit in spermatogonia to steer them down the differentiation path. "
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    ABSTRACT: Within the testis the spermatogonial stem cells reside in a unique microenvironment, or 'niche', which includes the surrounding somatic cells. The regulation of the balance between self-renewal and differentiation of spermatogonial stem cells determines the lifelong supply of spermatozoa by maintaining a population of undifferentiated spermatogonial stem cells and ensuring that adequate numbers of spermatogonia undergo spermatogenesis. Mouse models have been instrumental in determining a large number of factors involved in regulating the spermatogonial stem cell self-renewal and/or differentiation. However, the precise mechanisms controlling regulation of the germ cell niche remain to be elucidated. Recently the discovery of microRNAs, which regulate gene expression at the post-transcriptional level, have provided new insight into testis biology, spermatogenesis and germ stem cell regulation. In this review we summarize the main factors involved in the regulation of the germ stem cell niche and describe the role of microRNA signaling in this regulation.
    Full-text · Article · Apr 2014 · Seminars in Cell and Developmental Biology
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    • "RA promotes differentiation of SSCs to differentiated spermatogonia through several mechanisms. One such mechanism is the down-regulation of promyelocytic leukemia zinc finger (PLZF) [48], which is specifically expressed in SSCs and upon deletion in mice impairs spermatogonial differentiation by affecting the expression of genes involved in SSC self-renewal and differentiation [49] [50] [51] [52]. One function of PLZF is to repress the expression of c-kit in spermatogonia [53] and as RA downregulates PLZF in SSC this could be one mechanism that controls the up-regulation of c-kit in spermatogonia to steer them down the differentiation path. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Within the testis the spermatogonial stem cells reside in a unique microenvironment, or ‘niche’, which includes the surrounding somatic cells. The regulation of the balance between self-renewal and differentiation of spermatogonial stem cells determines the lifelong supply of spermatozoa by maintaining a population of undifferentiated spermatogonial stem cells and ensuring that adequate numbers of spermatogonia undergo spermatogenesis. Mouse models have been instrumental in determining a large number of factors involved in regulating the spermatogonial stem cell self-renewal and/or differentiation. However, the precise mechanisms controlling regulation of the germ cell niche remain to be elucidated. Recently the discovery of microRNAs, which regulate gene expression at the post-transcriptional level, have provided new insight into testis biology, spermatogenesis and germ stem cell regulation. In this review we summarize the main factors involved in the regulation of the germ stem cell niche and describe the role of microRNA signaling in this regulation.
    Full-text · Article · Jan 2014 · Seminars in Cell and Developmental Biology
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    • "Due to its importance for promoting expansion of differentiating spermatogonia, KIT expression in SSCs is subjected to a very tight transcriptional control. Promyelocytic Leukemia Zinc Finger (PLZF, also known as ZFP145, or ZBTB16) is a DNA sequence-specific transcriptional repressor that can exert local and long-range chromatin remodeling activity through the recruitment of DNA histone deacetylases and through the action of several nuclear corepressors (53). PLZF is specifically expressed in SSCs, and male PLZF knock-out (KO) mice show progressive spermatogonia depletion due to the deregulated expression of genes controlling the switch between self-renewal and differentiation (54–56). "
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