Brg1 Governs a Positive Feedback Circuit in the Hair Follicle for Tissue Regeneration and Repair

Xiong, Yiqin; Li, Wei; Shang, Ching; Chen, Richard M.; Han, Pei; Yang, Jin; Stankunas, Kryn; Wu, Bingruo; Pan, Minggui; Zhou, Bin; Longaker, Michael T.; Chang, Ching Pin

doi:10.1016/j.devcel.2013.03.015

Cited by 55 publications

(50 citation statements)

References 57 publications

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“…Loss of Jarid2 does not affect the number of bulge SCs, but delays the proliferation of HG and the more lineagerestricted progenitor cells, consequently delaying anagen entry. Brg1, a catalytic subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, maintains the bulge SCs and acts downstream of sonic hedgehog signaling to fuel hair growth (32). Together, these and our findings highlight the importance of tuning histone modifications, particularly the H3K27me3 and H3K4me3 marks, as well as ATP-dependent chromatin remodeling in HF SC biology.…”

Section: Discussionmentioning

confidence: 53%

Pygo2 regulates β-catenin–induced activation of hair follicle stem/progenitor cells and skin hyperplasia

Sun

Watanabe

Fallahi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Understanding the epigenetic mechanisms that control the activation of adult stem cells holds the promise of tissue and organ regeneration. Hair follicle stem cells have emerged as a prime model to study stem cell activation. Wnt/β-catenin signaling controls multiple aspects of skin epithelial regeneration, with its excessive activity promoting the hyperactivation of hair follicle stem/ progenitor cells and tumorigenesis. The contribution of chromatin factors in regulating Wnt/β-catenin pathway function in these processes is unknown. Here, we show that chromatin effector Pygopus homolog 2 (Pygo2) produced by the epithelial cells facilitates depilation-induced hair regeneration, as well as β-catenin-induced activation of hair follicle stem/early progenitor cells and trichofolliculoma-like skin hyperplasia. Pygo2 maximizes the expression of Wnt/β-catenin targets, but is dispensable for β-catenin-mediated expansion of LIM/homeobox protein Lhx2 + cells, in the stem/early progenitor cell compartment of the hair follicle. Moreover, β-catenin and Pygo2 converge to induce the accumulation and acetylation of tumor suppressor protein p53 upon the cell cycle entry of hair follicle early progenitor cells and in cultured keratinocytes. These findings identify Pygo2 as an important regulator of Wnt/ β-catenin function in skin epithelia and p53 activation as a prominent downstream event of β-catenin/Pygo2 action in stem cell activation.

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Section: Discussionmentioning

confidence: 53%

Pygo2 regulates β-catenin–induced activation of hair follicle stem/progenitor cells and skin hyperplasia

Sun

Watanabe

Fallahi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…However, in matrix cells, which contribute to the bulk of the hair shaft, NFκβ recruitment by BRG1 activates Shh to maintain hair growth. The loss of Brg1 or inhibition of SHH signaling disrupts this molecular circuitry, resulting in failure in hair regeneration and tissue repair (Wang et al, 2000;Xiong et al, 2013). Thus co-operation between chromatin remodelers, signaling pathways and transcription factors regulates mammalian hair development.…”

Section: Gltscr1mentioning

confidence: 99%

ATP-dependent chromatin remodeling during mammalian development

2016

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Precise gene expression ensures proper stem and progenitor cell differentiation, lineage commitment and organogenesis during mammalian development. ATP-dependent chromatin-remodeling complexes utilize the energy from ATP hydrolysis to reorganize chromatin and, hence, regulate gene expression. These complexes contain diverse subunits that together provide a multitude of functions, from early embryogenesis through cell differentiation and development into various adult tissues. Here, we review the functions of chromatin remodelers and their different subunits during mammalian development. We discuss the mechanisms by which chromatin remodelers function and highlight their specificities during mammalian cell differentiation and organogenesis.

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“…Deficiency in p63 leads to significant changes in the expression of many other genes involved in chromatin organisation and remodelling, including Brg1 (Fessing et al, 2011). Brg1 ablation is associated with alterations in epidermal barrier formation in embryonic skin, as well as with defects in hair follicle stem cell activity and hair loss in adult mice (Indra et al, 2005;Xiong et al, 2013). However, many aspects of the 3D genome organisation in epidermal progenitor cells, including the regulatory mechanisms that control higher-order chromatin remodelling during distinct stages of epidermal development, remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells

et al. 2014

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Chromatin structural states and their remodelling, including higher-order chromatin folding and three-dimensional (3D) genome organisation, play an important role in the control of gene expression. The role of 3D genome organisation in the control and execution of lineage-specific transcription programmes during the development and differentiation of multipotent stem cells into specialised cell types remains poorly understood. Here, we show that substantial remodelling of the higher-order chromatin structure of the epidermal differentiation complex (EDC), a keratinocyte lineage-specific gene locus on mouse chromosome 3, occurs during epidermal morphogenesis. During epidermal development, the locus relocates away from the nuclear periphery towards the nuclear interior into a compartment enriched in SC35-positive nuclear speckles. Relocation of the EDC locus occurs prior to the full activation of EDC genes involved in controlling terminal keratinocyte differentiation and is a lineage-specific, developmentally regulated event controlled by transcription factor p63, a master regulator of epidermal development. We also show that, in epidermal progenitor cells, p63 directly regulates the expression of the ATP-dependent chromatin remodeller Brg1, which binds to distinct domains within the EDC and is required for relocation of the EDC towards the nuclear interior. Furthermore, Brg1 also regulates gene expression within the EDC locus during epidermal morphogenesis. Thus, p63 and its direct target Brg1 play an essential role in remodelling the higher-order chromatin structure of the EDC and in the specific positioning of this locus within the landscape of the 3D nuclear space, as required for the efficient expression of EDC genes in epidermal progenitor cells during skin development.

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Brg1 Governs a Positive Feedback Circuit in the Hair Follicle for Tissue Regeneration and Repair

Cited by 55 publications

References 57 publications

Pygo2 regulates β-catenin–induced activation of hair follicle stem/progenitor cells and skin hyperplasia

Pygo2 regulates β-catenin–induced activation of hair follicle stem/progenitor cells and skin hyperplasia

ATP-dependent chromatin remodeling during mammalian development

p63 and Brg1 control developmentally regulated higher-order chromatin remodelling at the epidermal differentiation complex locus in epidermal progenitor cells

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