The ability of transcription factors and RNA polymerases to access specific promoters and transcribe genes is also regulated by the packaging of DNA by proteins and RNA, together forming the chromatin. Chromatin can package DNA tightly (heterochromatin) or loosely (euchromatin). In euchromatin, RNA polymerases can freely bind to DNA and genes are actively transcribed. In heterochromatin, DNA is tightly packaged, protected from the transcription machinery, sequestering genes away from transcription. The basic unit of chromatin is the nucleosome, which contains eight histone proteins packaging 146 base pairs of DNA. Histones can be extensively modified to regulate the accessibility of the DNA to the transcriptional apparatus (see Chapter 3). Histones can be chemically modified by acetylation, methylation, phosphorylation, or ubiquitination. In general, acetylation opens the nucleosome to increase transcription, whereas phosphorylation marks damaged DNA. Histone methylation can either open chromatin to increase transcription or close it to repress transcription, depending on where the histone is methylated. Transcription factors can themselves recruit histone-modifying enzymes that further regulate transcription. In hematopoiesis, transcription factors, including GATA-1, EKLF, NF-E2, and PU.1, recruit histone acetyltransferases (HATs) and histone deacetylases (HDACs) to promoters of their respective target genes, leading to addition or sub traction of acetyl groups from histones, that in turn alters chromatin structure and accessibility for transcription.[1] GATA-1, a gene essential to erythroid maturation and survival, directly recruits HAT complexes to the β-globin locus to stimulate transcription activation.

Chromatin remodeling is mediated by a family of proteins with switch/sucrose nonfermentable (SWI/SNF) domains. These proteins use adenosine triphosphate (ATP) hydrolysis to shift the nucleosome core along the length of the DNA, a process also known as nucleosome sliding. By sliding nucleosomes away from a gene sequence, SWI/ SNF complexes can activate gene transcription. SWI/SNF proteins also contain helicase enzyme activity, which unwinds the DNA by breaking hydrogen bonds between the complementary nucleotides on opposite strands. By unwinding the DNA into two single strands, the DNA can then be read by RNA polymerases in the direction 3′ to 5′, allowing RNA polymerase to produce an antiparallel RNA strand. The SWI/SNF complex has been shown to be active in the DNA damage response and is also responsible for tumor suppression. These processes are described in further detail in Chapter 2.

References
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[1] Xiang G, Keller CA, Heuston E, et al. An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis. Genome Res. 2020;30(3):472–484.

مواضيع ذات صلة

RNA Polymerase Binding and Regulation by Transcription Factors

The Discovery of Self-Splicing RNAs

Splicing Reactions and Complexes

آلية واهمية التحول

التحول transformation

Involvement of the U1 snRNP Particle in Splicing

البادئ (Promoter)

تضاعف الدنا

The Clinical Utility of Genomics in Hematologic Malignancies

The Discovery and Assay of RNA Splicing

Termination

Polymerase Elongation Rate