scholarly journals Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Pengfei Xu ◽  
Haoze V Yu ◽  
Kuo-Chang Tseng ◽  
Mackenzie Flath ◽  
Peter Fabian ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Specific Activity ◽  
Skeletal Development ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Cartilage Differentiation ◽  
The Face ◽  
Neural Crest Migration ◽  
Gain Access

The specification of cartilage requires Sox9, a transcription factor with broad roles for organogenesis outside the skeletal system. How Sox9 and other factors gain access to cartilage-specific cis-regulatory regions during skeletal development was unknown. By analyzing chromatin accessibility during the differentiation of neural crest cells into chondrocytes of the zebrafish head, we find that cartilage-associated chromatin accessibility is dynamically established. Cartilage-associated regions that become accessible after neural crest migration are co-enriched for Sox9 and Fox transcription factor binding motifs. In zebrafish lacking Foxc1 paralogs, we find a global decrease in chromatin accessibility in chondrocytes, consistent with a later loss of dorsal facial cartilages. Zebrafish transgenesis assays confirm that many of these Foxc1-dependent elements function as enhancers with region- and stage-specific activity in facial cartilages. These results show that Foxc1 promotes chondrogenesis in the face by establishing chromatin accessibility at a number of cartilage-associated gene enhancers.

scholarly journals Foxc1 establishes enhancer accessibility for craniofacial cartilage differentiation

2020 ◽  
Author(s):  
Pengfei Xu ◽  
Haoze Vincent Yu ◽  
Kuo-Chang Tseng ◽  
Mackenzie Flath ◽  
Peter Fabian ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Specific Activity ◽  
Skeletal Development ◽  
Chromatin Accessibility ◽  
List Type ◽  
Binding Motifs ◽  
Cartilage Differentiation ◽  
The Face ◽  
Neural Crest Migration

AbstractThe specification of cartilage requires Sox9, a transcription factor with broad roles for organogenesis outside the skeletal system. How Sox9 gains selective access to cartilage-specific cis-regulatory regions during skeletal development had remained unclear. By analyzing chromatin accessibility during the differentiation of neural crest cells into chondrocytes of the zebrafish head, we find that cartilage-associated chromatin accessibility is dynamically established. Cartilage-associated regions that become accessible after neural crest migration are co-enriched for Sox9 and Fox transcription factor binding motifs. In zebrafish lacking Foxc1 paralogs, we find a global decrease in chromatin accessibility in chondrocytes, consistent with a later loss of dorsal facial cartilages. Zebrafish transgenesis assays confirm that many of these Foxc1-dependent elements function as enhancers with region- and stage-specific activity in facial cartilages. We propose that Foxc1-dependent chromatin accessibility helps directs the versatile Sox9 protein to a chondrogenic program in the face.HighlightsDynamic chromatin accessibility across facial cartilage developmentCo-enrichment of Fox- and Sox-binding motifs in accessible regionsFoxc1 establishes accessibility in a subset of facial cartilage enhancersModular activity of Foxc1-dependent cartilage enhancers in zebrafish

scholarly journals LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Run Jin ◽  
Samantha Klasfeld ◽  
Yang Zhu ◽  
Meilin Fernandez Garcia ◽  
Jun Xiao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Fate ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Chromatin Remodelers ◽  
Pioneer Transcription Factor ◽  
Chromatin Reprogramming

AbstractMaster transcription factors reprogram cell fate in multicellular eukaryotes. Pioneer transcription factors have prominent roles in this process because of their ability to contact their cognate binding motifs in closed chromatin. Reprogramming is pervasive in plants, whose development is plastic and tuned by the environment, yet little is known about pioneer transcription factors in this kingdom. Here, we show that the master transcription factor LEAFY (LFY), which promotes floral fate through upregulation of the floral commitment factor APETALA1 (AP1), is a pioneer transcription factor. In vitro, LFY binds to the endogenous AP1 target locus DNA assembled into a nucleosome. In vivo, LFY associates with nucleosome occupied binding sites at the majority of its target loci, including AP1. Upon binding, LFY ‘unlocks’ chromatin locally by displacing the H1 linker histone and by recruiting SWI/SNF chromatin remodelers, but broad changes in chromatin accessibility occur later. Our study provides a mechanistic framework for patterning of inflorescence architecture and uncovers striking similarities between LFY and animal pioneer transcription factor.

scholarly journals LEAFY is a pioneer transcription factor and licenses cell reprogramming to floral fate

2020 ◽  
Author(s):  
Run Jin ◽  
Samantha Klasfeld ◽  
Meilin Fernandez Garcia ◽  
Jun Xiao ◽  
Soon-Ki Han ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cell Fate ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Chromatin Remodelers ◽  
Pioneer Transcription Factor ◽  
Chromatin Reprogramming

ABSTRACTMaster transcription factors reprogram cell fate in multicellular eukaryotes. Pioneer transcription factors have prominent roles in this process because of their ability to contact their cognate binding motifs in closed chromatin. Reprogramming is pervasive in plants, whose development is plastic and tuned by the environment, yet no bonafide pioneer transcription factor has - been identified in this kingdom. Here we show that the master transcription factor LEAFY (LFY), which promotes floral fate through upregulation of the floral commitment factor APETALA1 (AP1), is a pioneer transcription factor. In vitro, LFY binds in a sequence-specific manner and with high affinity to the endogenous AP1 target locus DNA assembled into a nucleosome. In vivo, LFY associates with nucleosome occupied binding sites at the majority of its target loci, including AP1, where it co-occupies DNA with histones. Moreover, the LFY DNA contact helix shares defining properties with those of strong nucleosome binding pioneer factors. At the AP1 locus, LFY unlocks chromatin locally by displacing the H1 linker histone and by recruiting SWI/SNF chromatin remodelers, but broad changes in chromatin accessibility occur later and require activity of additional, non-pioneer transcription, factors. Our study provides a mechanistic framework for patterning of inflorescence architecture and uncovers striking similarities between plant and animal pioneer transcription factors. Further analyses aimed at elucidating the defining characteristics of pioneer transcription factors will allow harnessing these for enhanced cell fate reprogramming.

scholarly journals A Bayesian approach for correcting Tn5 transposition bias in ATAC-seq footprinting

2019 ◽  
Author(s):  
Vinayak V Viswanadham ◽  
Vinay S Mahajan ◽  
Shiv Pillai
Keyword(s):  
Transcription Factor ◽  
Bayesian Approach ◽  
Bias Correction ◽  
Chromatin Accessibility ◽  
Binding Motifs ◽  
Naked Dna ◽  
Genome Wide ◽  
Transcription Factor Binding Motifs ◽  
Tn5 Transposase ◽  
Sequence Bias

ATAC-seq exploits the observation that the pattern of transposition of a hyperactive Tn5 transposase in native chromatin mirrors genome-wide chromatin accessibility. It has been suggested that transposition observed around transcription factor binding motifs can be used to assess their occupancy in the form of footprints. However, we show that the vast majority of footprints observed at transcription factor motifs in ATAC-seq data spuriously arise from the intrinsic sequence-dependent transposition site bias of Tn5 and are also observed in naked DNA. We demonstrate that the Tn5 transposition bias can be corrected using existing tools for sequence bias correction and a novel estimate of global occupancy in order to produce more reliable estimates of footprints.

scholarly journals Program Specificity for Ptf1a in Pancreas versus Neural Tube Development Correlates with Distinct Collaborating Cofactors and Chromatin Accessibility

2013 ◽  
Vol 33 (16) ◽  
pp. 3166-3179 ◽  
Author(s):  
David M. Meredith ◽  
Mark D. Borromeo ◽  
Tye G. Deering ◽  
Bradford H. Casey ◽  
Trisha K. Savage ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neural Tube ◽  
Gene Families ◽  
Chromatin Accessibility ◽  
Open Chromatin ◽  
Binding Motifs ◽  
Helix Loop Helix ◽  
Neural Tube Development ◽  
Genomic Regions

The lineage-specific basic helix-loop-helix transcription factor Ptf1a is a critical driver for development of both the pancreas and nervous system. How one transcription factor controls diverse programs of gene expression is a fundamental question in developmental biology. To uncover molecular strategies for the program-specific functions of Ptf1a, we identified bound genomic regionsin vivoduring development of both tissues. Most regions bound by Ptf1a are specific to each tissue, lie near genes needed for proper formation of each tissue, and coincide with regions of open chromatin. The specificity of Ptf1a binding is encoded in the DNA surrounding the Ptf1a-bound sites, because these regions are sufficient to direct tissue-restricted reporter expression in transgenic mice. Fox and Sox factors were identified as potential lineage-specific modifiers of Ptf1a binding, since binding motifs for these factors are enriched in Ptf1a-bound regions in pancreas and neural tube, respectively. Of the Fox factors expressed during pancreatic development, Foxa2 plays a major role. Indeed, Ptf1a and Foxa2 colocalize in embryonic pancreatic chromatin and can act synergistically in cell transfection assays. Together, these findings indicate that lineage-specific chromatin landscapes likely constrain the DNA binding of Ptf1a, and they identify Fox and Sox gene families as part of this process.

scholarly journals Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hyo Sik Jang ◽  
Yujie Chen ◽  
Jiaxin Ge ◽  
Alicia N. Wilkening ◽  
Yiran Hou ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Neural Crest ◽  
Cell Fate ◽  
Pigment Cell ◽  
Chromatin Accessibility ◽  
Pigment Cells ◽  
Epigenetic Landscape ◽  
Cell Fate Decisions ◽  
Neural Crest Differentiation

Abstract Background Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood. Results We chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and iridophores to identify epigenetic determinants shaping cell type-specific gene expression. Motif enrichment in the epigenetically dynamic regions reveals putative transcription factors that might be responsible for driving pigment cell identity. Through this effort, in the relatively uncharacterized iridophores, we validate alx4a as a necessary and sufficient transcription factor for iridophore differentiation and present evidence on alx4a’s potential regulatory role in guanine synthesis pathway. Conclusions Pigment cell fate is marked by substantial DNA demethylation events coupled with dynamic chromatin accessibility to potentiate gene regulation through cis-regulatory control. Here, we provide a multi-omic resource for neural crest differentiation into melanophores and iridophores. This work led to the discovery and validation of iridophore-specific alx4a transcription factor.

scholarly journals Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation

2020 ◽  
Vol 8 ◽  
Author(s):  
Qian Liu ◽  
Mao Li ◽  
Shiyi Wang ◽  
Zhousheng Xiao ◽  
Yuanyuan Xiong ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Formation ◽  
Osteoblast Differentiation ◽  
Bone Mineralization ◽  
Skeletal Development ◽  
Intramembranous Bone ◽  
Cartilage Differentiation ◽  
New Research ◽  
Intramembranous Bone Formation

With increasing life expectations, more and more patients suffer from fractures either induced by intensive sports or other bone-related diseases. The balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption is the basis for maintaining bone health. Osterix (Osx) has long been known to be an essential transcription factor for the osteoblast differentiation and bone mineralization. Emerging evidence suggests that Osx not only plays an important role in intramembranous bone formation, but also affects endochondral ossification by participating in the terminal cartilage differentiation. Given its essentiality in skeletal development and bone formation, Osx has become a new research hotspot in recent years. In this review, we focus on the progress of Osx’s function and its regulation in osteoblast differentiation and bone mass. And the potential role of Osx in developing new therapeutic strategies for osteolytic diseases was discussed.

Sign in / Sign up

Export Citation Format

Share Document