Basic Helix-Loop-Helix Transcription Factors

Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Author(s): 
Kahn, Arnold J.
Publication Title: 
Cell Metabolism

Iron regulatory proteins (Irps) 1 and 2 posttranscriptionally control the expression of transcripts that contain iron-responsive element (IRE) sequences, including ferritin, ferroportin, transferrin receptor, and hypoxia-inducible factor 2? (HIF2?). We report here that mice with targeted deletion of Irp1 developed pulmonary hypertension and polycythemia that was exacerbated by a low-iron diet. Hematocrits increased to 65% in iron-starved mice, and many polycythemic mice died of abdominal hemorrhages. Irp1 deletion enhanced HIF2?

Author(s): 
Ghosh, Manik C.
Zhang, De-Liang
Jeong, Suh Young
Kovtunovych, Gennadiy
Ollivierre-Wilson, Hayden
Noguchi, Audrey
Tu, Tiffany
Senecal, Thomas
Robinson, Gabrielle
Crooks, Daniel R.
Tong, Wing-Hang
Ramaswamy, Kavitha
Singh, Anamika
Graham, Brian B.
Tuder, Rubin M.
Yu, Zu-Xi
Eckhaus, Michael
Lee, Jaekwon
Springer, Danielle A.
Rouault, Tracey A.
Publication Title: 
Nature Communications

Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination.

Author(s): 
Lapierre, Louis R.
De Magalhaes Filho, C. Daniel
McQuary, Philip R.
Chu, Chu-Chiao
Visvikis, Orane
Chang, Jessica T.
Gelino, Sara
Ong, Binnan
Davis, Andrew E.
Irazoqui, Javier E.
Dillin, Andrew
Hansen, Malene
Publication Title: 
Epigenetics

Epigenetic modifications to peripheral white blood cell DNA occur in response to a wide variety of exposures. In prior work, we and others have shown that broad changes in DNA methylation, particularly at the aryl hydrocarbon receptor repressor (AHRR) locus, occur in samples from subjects with long histories of smoking. However, given the large number of epigenetic changes that occur in response to prolonged smoking, the primacy of the response at AHRR and the sensitivity of these changes to low levels of smoking are not known.

Author(s): 
Philibert, Robert A.
Beach, Steven R. H.
Brody, Gene H.
Publication Title: 
Nature Neuroscience

Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis-affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The transcriptional consequences of differential DNA methylation were further defined by genome-wide RNA-sequencing analysis and validated in two independent cohorts.

Author(s): 
Huynh, Jimmy L.
Garg, Paras
Thin, Tin Htwe
Yoo, Seungyeul
Dutta, Ranjan
Trapp, Bruce D.
Haroutunian, Vahram
Zhu, Jun
Donovan, Michael J.
Sharp, Andrew J.
Casaccia, Patrizia
Publication Title: 
Human Molecular Genetics

To investigate epigenetic contributions to Huntington's disease (HD) pathogenesis, we carried out genome-wide mapping of the transcriptional mark, trimethyl-histone H3-lysine 4 (H3K4me3) in neuronal nuclei extracted from prefrontal cortex of HD cases and controls using chromatin immunoprecipitation followed by deep-sequencing.

Author(s): 
Bai, Guang
Cheung, Iris
Shulha, Hennady P.
Coelho, Joana E.
Li, Ping
Dong, Xianjun
Jakovcevski, Mira
Wang, Yumei
Grigorenko, Anastasia
Jiang, Yan
Hoss, Andrew
Patel, Krupal
Zheng, Ming
Rogaev, Evgeny
Myers, Richard H.
Weng, Zhiping
Akbarian, Schahram
Chen, Jiang-Fan
Publication Title: 
Epigenetics

Epigenetic mechanisms can mediate gene-environment interactions relevant for complex disorders. The BDNF gene is crucial for development and brain plasticity, is sensitive to environmental stressors, such as hypoxia, and harbors the functional SNP rs6265 (Val(66)Met), which creates or abolishes a CpG dinucleotide for DNA methylation.

Author(s): 
Ursini, Gianluca
Cavalleri, Tommaso
Fazio, Leonardo
Angrisano, Tiziana
Iacovelli, Luisa
Porcelli, Annamaria
Maddalena, Giancarlo
Punzi, Giovanna
Mancini, Marina
Gelao, Barbara
Romano, Raffaella
Masellis, Rita
Calabrese, Francesca
Rampino, Antonio
Taurisano, Paolo
Di Giorgio, Annabella
Keller, Simona
Tarantini, Letizia
Sinibaldi, Lorenzo
Quarto, Tiziana
Popolizio, Teresa
Caforio, Grazia
Blasi, Giuseppe
Riva, Marco A.
De Blasi, Antonio
Chiariotti, Lorenzo
Bollati, Valentina
Bertolino, Alessandro
Publication Title: 
Stem Cells (Dayton, Ohio)

Human embryonic stem cells (hESCs) have been reported to exert cytoprotective activity in the area of tissue injury. However, hypoxia/oxidative stress prevailing in the area of injury could activate p53, leading to death and differentiation of hESCs. Here we report that when exposed to hypoxia/oxidative stress, a small fraction of hESCs, namely the SSEA3+/ABCG2+ fraction undergoes a transient state of reprogramming to a low p53 and high hypoxia inducible factor (HIF)-2? state of transcriptional activity.

Author(s): 
Das, Bikul
Bayat-Mokhtari, Reza
Tsui, Micky
Lotfi, Shamim
Tsuchida, Rika
Felsher, Dean W.
Yeger, Herman
Publication Title: 
Stem Cell Research & Therapy

Human embryonic stem cells (hESCs) have been reported to confer cytoprotection in the context of tissue injury. This is somewhat counterintuitive given that microenvironmental factors such as hypoxia and oxidative stress may activate p53 and result in death and differentiation of these hESCs. In this article, we discuss a novel mechanism through which hESCs can be re-programmed (through exposure to hypoxia/oxidative stress) to transiently suppress p53, enhance 'stemness', and exist in a highly cytoprotective and undifferentiated state.

Author(s): 
Cummins, Eoin P.
Publication Title: 
Oncogene

Human differentially expressed in chondrocytes (DEC), mouse stimulated with retinoic acid and rat split and hairy related proteins constitute a structurally distinct class of the basic helix-loop-helix proteins. DEC1 is abundantly expressed in tumors and protects against apoptosis induced by serum starvation. In this study, we report that DEC1 antiapoptosis is achieved by inducing survivin, an antiapoptotic protein. In paired tumor-normal tissues, survivin and DEC1 exhibited a paralleled expression pattern.

Author(s): 
Li, Y.
Xie, M.
Yang, J.
Yang, D.
Deng, R.
Wan, Y.
Yan, B.

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