Survey of variation in human transcription factors reveals prevalent DNA binding changes-Reference-Cited by-同舟云学术

Survey of variation in human transcription factors reveals prevalent DNA binding changes

Published:2016-03-25 Issue:6280 Volume:351 Page:1450-1454
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Barrera Luis A.¹²³⁴,Vedenko Anastasia¹,Kurland Jesse V.¹,Rogers Julia M.¹²,Gisselbrecht Stephen S.¹,Rossin Elizabeth J.³⁵⁶,Woodard Jaie¹²,Mariani Luca¹,Kock Kian Hong¹⁷,Inukai Sachi¹,Siggers Trevor¹,Shokri Leila¹,Gordân Raluca¹,Sahni Nidhi⁸⁹¹⁰,Cotsapas Chris⁵⁶,Hao Tong⁸⁹¹⁰,Yi Song⁸⁹¹⁰,Kellis Manolis⁴⁶,Daly Mark J.⁵⁶¹¹,Vidal Marc⁸⁹¹⁰,Hill David E.⁸⁹¹⁰,Bulyk Martha L.¹²³⁶⁷

Affiliation:

1. Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.

2. Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, MA 02138, USA.

3. Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.

4. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

5. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

6. Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA.

7. Program in Biological and Biomedical Sciences, Harvard University, Cambridge, MA 02138, USA.

8. Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, MA 02215, USA.

9. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

10. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

11. Center for Human Genetics Research and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA.

Abstract

Variation and transcription factor binding Little is known about the phenotypic and functional effects of genetic variants that result in amino acid changes within functional proteins. Barrera et al. investigated whether amino acid variants changed the DNA binding specificity or affinity of transcription factors. Predictive analyses identified changes in the proteins, and protein-binding microarrays verified changes that affected transcription factor function, including those associated with disease. Thus, within-human protein sequence variation can affect transcriptional regulatory networks, which, depending on the genetic variant, may confer robustness and buffer against amino acid changes and could explain phenotypic variation among individuals. Science , this issue p. 1450

Funder

National Institutes of Health

A*STAR National Science Scholarship

National Science Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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