Extensive binding of poorly characterized human transcription factors to genomic dark matter
Abstract
Abstract The functional impact of a large portion of the human genome known as “dark matter DNA”, which is composed mainly of repeat sequences, remains unknown. The genome also encodes many putative and poorly characterized transcription factors. Here, we determine genomic binding locations of 166 poorly characterized human transcription factors in living cells. Nearly half of them associate strongly with known regulatory regions such as promoters and enhancers, frequently co-localizing with each other at conserved motif matches. The other half often associate with genomic dark matter, however, at largely non-overlapping (i.e., unique) sites, via intrinsic sequence recognition. Fifty-four of the latter half, which we term dark transcription factors , mainly bind within regions of closed chromatin, with each recognizing a unique set of repeat sequences. The dark transcription factors include many KZNFs, which are known to bind and silence transposable elements, and other transcription factors with apparent repressive functions. Others may be pioneer transcription factors. For example, we find that induction of TPRX1, a known regulator of zygotic preimplantation, leads to chromatin opening at many of its binding sites in the dark matter genome.
Article Details
Authors (51)
Rozita Razavi
Ali Fathi
Isaac Yellan
Alexander Brechalov
Kaitlin U. Laverty
Arttu Jolma
Aldo Hernandez-Corchado
Hong Zheng
Center of Nanomaterials for Renewable Energy, State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering
Ally W. H. Yang
Mihai Albu
Marjan Barazandeh
Chun Hu
Ilya E. Vorontsov
Zain M. Patel
Bart Deplancke
Oriol Fornes
Jan Grau
Ivo Grosse
Fedor A. Kolpakov
Vsevolod J. Makeev
Zhenfeng Deng
Samuel A. Lambert
Sara E. Pour
Mikhail Salnikov
Georgy Meshcheryakov
Giovanna Ambrosini
Antoni J. Gralak
Sachi Inukai
Judith F. Kribelbauer-Swietek
Marie-Luise Plescher
Semyon Kolmykov
Ivan Yevshin
Nikita Gryzunov
Ivan Kozin
Mikhail Nikonov
Vladimir Nozdrin
Arsenii Zinkevich
Katerina Faltejskova
Pavel Kravchenko
Sergey Abramov
Alexandr Boytsov
Vasilii Kamenets
Dmitry Penzar
Anton Vlasov
Xiaoting Chen
Matthew T. Weirauch
Division of Gastroenterology, Hepatology & Nutrition, Cincinnati Children’s Hospital Medical Center
Ivan V. Kulakovskiy
Philipp Bucher
Quaid Morris
Hamed S. Najafabadi
Timothy R. Hughes